Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies

PubMed Central

McGettigan, Patricia; Henry, David

2011-01-01

Background Randomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings. Methods and Findings We performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR) estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study) analyses, generating ratios of RRs (RRRs). Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies), the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59), and diclofenac, 1.40 (1.27, 1.55), and the lowest with ibuprofen, 1.18 (1.11, 1.25), and naproxen, 1.09 (1.02, 1.16). In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57), celecoxib, 1.26 (1.09, 1.47), and diclofenac, 1.22 (1.12, 1.33), and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88), etodolac, 1.55 (1.28, 1.87), and indomethacin, 1.30 (1.19, 1.41), had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR = 1.68 (99% CI 1.14, 2.49), and naproxen, RRR = 1.75 (1.16, 2.64); etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR = 0.92 (0.87, 0.99). RR estimates were constant with different background risks for

Celecoxib and sulfasalazine had negative association with coronary artery diseases in patients with ankylosing spondylitis

PubMed Central

Wu, Li-Chih; Leong, Pui-Ying; Yeo, Kai-Jieh; Li, Ting-Yu; Wang, Yu-Hsun; Chiou, Jeng-Yuan; Wei, James Cheng-Chung

2016-01-01

Abstract The aim of the study is to assess the effects of celecoxib and sulfasalazine on the risk of coronary artery disease (CAD) in patients with ankylosing spondylitis (AS). Using the claims data of Taiwan National Health Insurance (NHI) database, a nationally representative data that contain the medical records of 23 million Taiwan residents, we randomly selected 1 million cohort from the database, and then we enrolled only patients who were newly diagnosed with AS (n = 4829) between year 2001 and 2010, excluding patients who had CAD (ICD-9- CM codes: 410–414) before the diagnosis of AS (n = 4112). According to propensity score matched 1:2 on age, gender, AS duration, Charlson comorbidity index, hypertension, and hyperlipidemia, 236 and 472 patients were included in the case (AS with CAD) and control (AS without CAD) groups, respectively. We used the WHO defined daily dose (DDD) as a tool to assess the dosage of sulfasalazine and celecoxib exposure. Conditional logistic regression was used to estimate the crude and adjusted odds ratios (ORs) and 95% confidence interval (CI) for the risk of CAD associated with use of sulfasalazine and celecoxib. Among 4112 AS patients, 8.4% (346/4112) developed CAD. CAD in AS patients were positively associated with age of 35 to 65, Charlson comorbidities index (CCI), hypertension, and hyperlipidemia. There was no gender difference between case and control groups. After adjustment for age, gender, CCI, hypertension, and hyperlipidemia, sulfasalazine users with an average daily dose ≥ 0.5 DDD (0.5 gm/day) had negative association with CAD events as compared to sulfasalazine nonusers (OR 0.63; 95% CI, 0.40–0.99, P < 0.05). NSAIDs, including celecoxib, etoricoxib, but no naproxen and diclofenac were negatively associated with CAD. Celecoxib users, with an average daily dose > 1.5 DDD, were negatively associated with CAD events, compared to celecoxib nonusers (OR 0.34; 95% CI, 0.13–0.89; P < 0.05). In this 10-year

Examination of the effect of increasing doses of etoricoxib on oral methotrexate pharmacokinetics in patients with rheumatoid arthritis.

PubMed

Schwartz, Jules I; Agrawal, Nancy G B; Wong, P H; Miller, Jutta; Bachmann, Kenneth; Marbury, Thomas; Hoelscher, David; Cavanaugh, Paul F; Gottesdiener, Keith

2009-10-01

The authors designed 2 randomized controlled studies to examine the effects of etoricoxib 60 to 120 mg daily on methotrexate pharmacokinetics in 50 rheumatoid arthritis (RA) patients on stable doses of methotrexate (7.5-20 mg). Patients received oral methotrexate at baseline and on days 7 and 14. In study 1, patients received etoricoxib 60 mg (days 1-7) and then 120 mg (days 8-14); in study 2, patients received etoricoxib 90 mg (days 1-7) and then 120 mg (days 8-14). For study 1, the AUC(0-infinity) geometric mean ratio (GMR) (90% confidence interval [CI]) for day 7 versus baseline was 1.01 (0.91, 1.12) for etoricoxib 60 mg; the area under the plasma concentration-time curve from zero to infinity (AUC(0-infinity)) GMR (90% CI) for day 14 was 1.28 (1.15, 1.42) for etoricoxib 120 mg. For study 2, the AUC(0-infinity) GMR (90% CI) for day 7 versus baseline was 1.07 (1.01, 1.13) for etoricoxib 90 mg; the AUC(0-infinity) GMR (90% CI) for day 14 was 1.05 (0.99, 1.11) for etoricoxib 120 mg. In summary, etoricoxib 60 and 90 mg had no effect on methotrexate plasma concentrations. Although no effect on methotrexate pharmacokinetics was observed with etoricoxib 120 mg in study 2, GMR AUC(0-infinity) fell outside the prespecified bounds in study 1. Standard monitoring of methotrexate-related toxicity should be continued when etoricoxib and methotrexate are administered concurrently, especially with doses >90 mg etoricoxib.

Etoricoxib - preemptive and postoperative analgesia (EPPA) in patients with laparotomy or thoracotomy - design and protocols

PubMed Central

2010-01-01

Background and Objective Our objective was to report on the design and essentials of the Etoricoxib protocol- Preemptive and Postoperative Analgesia (EPPA) Trial, investigating whether preemptive analgesia with cox-2 inhibitors is more efficacious than placebo in patients who receive either laparotomy or thoracotomy. Design and Methods The study is a 2 × 2 factorial armed, double blinded, bicentric, randomised placebo-controlled trial comparing (a) etoricoxib and (b) placebo in a pre- and postoperative setting. The total observation period is 6 months. According to a power analysis, 120 patients scheduled for abdominal or thoracic surgery will randomly be allocated to either the preemptive or the postoperative treatment group. These two groups are each divided into two arms. Preemptive group patients receive etoricoxib prior to surgery and either etoricoxib again or placebo postoperatively. Postoperative group patients receive placebo prior to surgery and either placebo again or etoricoxib after surgery (2 × 2 factorial study design). The Main Outcome Measure is the cumulative use of morphine within the first 48 hours after surgery (measured by patient controlled analgesia PCA). Secondary outcome parameters include a broad range of tests including sensoric perception and genetic polymorphisms. Discussion The results of this study will provide information on the analgesic effectiveness of etoricoxib in preemptive analgesia and will give hints on possible preventive effects of persistent pain. Trial registration NCT00716833 PMID:20504378

Evidence for a central mode of action for etoricoxib (COX-2 inhibitor) in patients with painful knee osteoarthritis.

PubMed

Arendt-Nielsen, Lars; Egsgaard, Line Lindhardt; Petersen, Kristian Kjær

2016-08-01

The COX-2 inhibitor etoricoxib modulates the peripheral and central nociceptive mechanisms in animals. This interaction has not been studied in patients with pain. This randomized, double-blind, placebo-controlled, 2-way crossover, 4-week treatment study investigated the pain mechanisms modulated by etoricoxib in patients with painful knee osteoarthritis. Patients were randomized to group A (60 mg/d etoricoxib followed by placebo) or B (placebo followed by 60 mg/d etoricoxib). The quantitative, mechanistic pain biomarkers were pressure pain thresholds, temporal summation (TS), and conditioning pain modulation. Clinical readouts were Brief Pain Inventory, WOMAC, painDETECT questionnaire (PD-Q), and time and pain intensity during walking and stair climbing. Etoricoxib as compared with placebo significantly modulated the pressure pain thresholds (P = 0.012, localized sensitization) at the knee and leg (control site) (P = 0.025, spreading sensitization) and TS assessed from the knee (P = 0.038) and leg (P = 0.045). Conditioning pain modulation was not modulated. The Brief Pain Inventory (pain scores), PD-Q, WOMAC, and walking and stair climbing tests were all significantly improved by etoricoxib. Based on a minimum of 30% or 50% pain alleviation (day 0-day 28), responders and nonresponders were defined. The nonresponders showed a significant association between increased facilitation of TS and increased pain alleviation. None of the other parameters predicted the degree of pain alleviation. Generally, a responder to etoricoxib has the most facilitated TS. In conclusion, etoricoxib (1) modulated central pain modulatory mechanisms and (2) improved pain and function in painful osteoarthritis. Stronger facilitation of TS may indicate a better response to etoricoxib, supporting the central mode-of-action of the drug.

A case report on toxic epidermal necrolysis with etoricoxib

PubMed Central

Kameshwari, J. S.; Devde, Raju

2015-01-01

Etoricoxib is a selective cyclo-oxygenase 2 (COX-2) enzyme inhibitor and is exploited for its analgesic activity in various disease conditions like osteoarthritis, gouty arthritis, acute pain including postoperative dental pain and primary dysmenorrhea, etc. Although highly efficacious in pain management the safety profile of this COX-2 inhibitor is yet to be established in a broader sense. Short-term clinical trials and postmarketing surveillance have shown a very rare incidence of very serious skin reactions like Steven Johnson syndrome or toxic epidermal necrolysis (TEN). In this case report, we summarize regarding a patient who developed TEN after treatment with etoricoxib for osteoarthritis that later resolved in 15 days after withdrawal and symptomatic treatment. PMID:25878388

Inhibitory effect of selective cyclooxygenase-2 inhibitor etoricoxib on human organic anion transporter 3 (hOAT3).

PubMed

Honjo, Hiroaki; Uwai, Yuichi; Iwamoto, Kikuo

2011-04-01

It is well known that nonsteroidal anti-inflammatory drugs (NSAIDs) delay the elimination of methotrexate. One of the mechanisms is thought to be inhibition of methotrexate uptake via human organic anion transporter 3 (hOAT3, SLC22A8) in the renal proximal tubule by NSAIDs. In this study, we evaluated the inhibitory effects of selective cyclooxygenase-2 inhibitor etoricoxib on hOAT3 by uptake experiments using Xenopus laevis oocytes. The injection of hOAT3 cRNA stimulated the uptake of methotrexate into the oocytes, and its transport was inhibited by etoricoxib. Etoricoxib inhibited estrone sulfate uptake by hOAT3 dose dependently, and the 50% inhibitory concentration was estimated to be 9.8 µM. Eadie-Hofstee plot analysis showed that etoricoxib inhibited hOAT3 in a competitive manner. These findings show that etoricoxib has inhibitory effect on hOAT3, and that the potential is comparable to that of traditional NSAIDs. ©2011 Bentham Science Publishers Ltd.

Further assessment of the clinically effective dose range of etoricoxib: a randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis.

PubMed

Greenwald, M; Peloso, P M; Mandel, D; Soto, O; Mehta, A; Frontera, N; Boice, J A; Zhan, X J; Curtis, S P

2011-10-01

To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA). RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences. Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p < 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p < 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0). The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients. Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.

Density functional theory studies of etoricoxib

NASA Astrophysics Data System (ADS)

Sachdeva, Ritika; Kaur, Prabhjot; Singh, V. P.; Saini, G. S. S.

2016-05-01

Etoricoxib is a COX-2 selective inhibitor drug with molecular formula C18H15ClN2O2S. It is primarily used for the treatment of arthritis(rheumatoid, psoriatic, osteoarthritis), ankylosing spondylitis, gout and chronic low back pain. Theoretical studies of the molecule including geometry optimization and vibrational frequency calculations were carried out with the help of density functional theory calculations using 6-311++ g (d, p) basis set and B3LYP functional.

Bioavailability of ibuprofen following oral administration of standard ibuprofen, sodium ibuprofen or ibuprofen acid incorporating poloxamer in healthy volunteers

PubMed Central

2009-01-01

Background The aim of this study was to compare the pharmacokinetic properties of sodium ibuprofen and ibuprofen acid incorporating poloxamer with standard ibuprofen acid tablets. Methods Twenty-two healthy volunteers were enrolled into this randomised, single-dose, 3-way crossover, open-label, single-centre, pharmacokinetic study. After 14 hours' fasting, participants received a single dose of 2 × 200 mg ibuprofen acid tablets (standard ibuprofen), 2 × 256 mg ibuprofen sodium dihydrate tablets (sodium ibuprofen; each equivalent to 200 mg ibuprofen acid) and 2 × 200 mg ibuprofen acid incorporating 60 mg poloxamer 407 (ibuprofen/poloxamer). A washout period of 2-7 days separated consecutive dosing days. On each of the 3 treatment days, blood samples were collected post dose for pharmacokinetic analyses and any adverse events recorded. Plasma concentration of ibuprofen was assessed using a liquid chromatographic-mass spectrometry procedure in negative ion mode. A standard statistical ANOVA model, appropriate for bioequivalence studies, was used and ratios of 90% confidence intervals (CIs) were calculated. Results Tmax for sodium ibuprofen was less than half that of standard ibuprofen (median 35 min vs 90 min, respectively; P = 0.0002) and Cmax was significantly higher (41.47 μg/mL vs 31.88 μg/mL; ratio test/reference = 130.06%, 90% CI 118.86-142.32%). Ibuprofen/poloxamer was bioequivalent to the standard ibuprofen formulation, despite its Tmax being on average 20 minutes shorter than standard ibuprofen (median 75 mins vs 90 mins, respectively; P = 0.1913), as the ratio of test/reference = 110.48% (CI 100.96-120.89%), which fell within the 80-125% limit of the CPMP and FDA guidelines for bioequivalence. The overall extent of absorption was similar for the three formulations, which were all well tolerated. Conclusion In terms of Tmax, ibuprofen formulated as a sodium salt was absorbed twice as quickly as from standard ibuprofen acid. The addition of poloxamer to

A randomized, clinical trial to assess the relative efficacy and tolerability of two doses of etoricoxib versus naproxen in patients with ankylosing spondylitis.

PubMed

Balazcs, Eva; Sieper, Joachim; Bickham, Kara; Mehta, Anish; Frontera, Nancy; Stryszak, Paul; Popmihajlov, Zoran; Peloso, Paul M

2016-10-13

This study evaluated two doses of etoricoxib (60 and 90 mg) vs. naproxen 1000 mg in subjects with ankylosing spondylitis (AS). This was a 2-part, double-blind, active comparator-controlled non-inferiority study in subjects ≥18 years of age with AS. In Part I, subjects were randomized to naproxen 1000 mg; etoricoxib 60 mg, and 90 mg. In Part II, naproxen and etoricoxib 90 mg subjects continued on the same treatment; subjects on etoricoxib 60 mg either continued on 60 mg or escalated to 90 mg. Part I (6 weeks) assessed the efficacy of A) etoricoxib 60 mg vs. naproxen and B) 90 mg vs. naproxen according to the time-weighted average change from baseline in Spinal Pain Intensity (SPI; 0-100 mm VAS) (primary endpoint). The non-inferiority margin was set at 8 mm for SPI. In Part II (20 weeks) we evaluated the potential benefit of increasing from 60 to 90 mg (predefined minimum clinically important difference = 6 mm in SPI) for inadequate responders (<50 % improvement from baseline in SPI) on etoricoxib 60 mg in Part I. In total, 1015 subjects were randomized to receive etoricoxib 60 mg (N = 702), etoricoxib 90 mg (N = 156), and naproxen 1000 mg (N = 157); 70.9 % were male and the mean age was 45.2 years. There were 919 subjects who completed Part I and all continued to Part II. In Part I, SPI change was non-inferior for both etoricoxib doses vs. naproxen. In both Part I and II, the incidence of adverse events (AEs), drug-related AEs, and serious adverse events (SAEs) were similar between the 3 treatment groups. Both doses of etoricoxib were non-inferior to naproxen. All treatments were well tolerated. Etoricoxib 60 and 90 mg effectively control pain in patients with AS, with 60 mg once daily as the lowest effective dose for most patients. Clinical Trials Registry # NCT01208207 . Registered on 22 September 2010.

Need for common internal controls when assessing the relative efficacy of pharmacologic agents using a meta-analytic approach: case study of cyclooxygenase 2-selective inhibitors for the treatment of osteoarthritis.

PubMed

Lee, Chin; Hunsche, Elke; Balshaw, Robert; Kong, Sheldon X; Schnitzer, Thomas J

2005-08-15

To evaluate the role of common internal controls in a meta-analysis of the relative efficacy of cyclooxygenase 2-selective inhibitors (coxibs) in the treatment of osteoarthritis (OA). A systematic search of Medline and US Food and Drug Administration electronic databases was performed to identify randomized, placebo-controlled clinical trials of coxibs (etoricoxib, celecoxib, rofecoxib, valdecoxib) in patients with hip and/or knee OA. The effect size for coxibs and common active internal controls (nonsteroidal antiinflammatory drugs [NSAIDs], naproxen) were determined by the mean changes from baseline in Western Ontario and McMaster Universities Osteoarthritis Index pain subscores as compared with placebo. The effect size for all coxib groups combined (0.44) indicated greater efficacy as compared with placebo, but significant heterogeneity (P < 0.0001) was observed. Rofecoxib at dosages of 12.5 mg/day and 25 mg/day and etoricoxib at a dosage of 60 mg/day had similar effect sizes (0.68 and 0.73, respectively), but these effect sizes were comparatively greater than those for both celecoxib at dosages of 200 mg/day and 100 mg twice daily or valdecoxib at a dosage of 10 mg/day (0.26 and 0.16, respectively). The effect sizes for NSAIDs or naproxen versus placebo, as determined using data from rofecoxib/etoricoxib trials, were consistently higher than the effect sizes derived from trials of celecoxib/valdecoxib. Significant heterogeneity was present in the overall effect size for NSAIDs (P = 0.007) and naproxen (P = 0.04) groups based on data available from all coxib trials. Coxibs and common active internal controls showed larger effect sizes versus placebo in the rofecoxib/etoricoxib trials than in the celecoxib/valdecoxib trials. These findings suggest systematic differences among published coxib trials and emphasize the need for direct-comparison trials. In the absence of such trials, common internal controls should be assessed when performing indirect meta

Reactivity of etoricoxib based on computational study of molecular orbitals, molecular electrostatic potential surface and Mulliken charge analysis

NASA Astrophysics Data System (ADS)

Sachdeva, Ritika; Soni, Abhinav; Singh, V. P.; Saini, G. S. S.

2018-05-01

Etoricoxib is one of the selective cyclooxygenase inhibitor drug which plays a significant role in the pharmacological management of arthritis and pain. The theoretical investigation of its reactivity is done using Density Functional Theory calculations. Molecular Electrostatic Potential Surface of etoricoxib and its Mulliken atomic charge distribution are used for the prediction of its electrophilic and nucleophilic sites. The detailed analysis of its frontier molecular orbitals is also done.

Use of cyclo-oxygenase 2 inhibitors (COX-2) and prescription non-steroidal anti-inflammatory drugs (NSAIDS) in UK and USA populations. Implications for COX-2 cardiovascular profile.

PubMed

Arellano, Félix M; Yood, Marianne Ulcickas; Wentworth, Charles E; Oliveria, Susan A; Rivero, Elena; Verma, Anila; Rothman, Kenneth J

2006-12-01

COX-2 and NSAIDS differ in their gastrointestinal (GI) and cardiovascular (CV) toxicity from pharmacological, clinical and epidemiologic point of views. Describe the patterns of use of NSAIDS and COX-2 in The Health Improvement Network (THIN) database in UK and the PharMetrics database in USA. We examined the experience of 10 distinct cohorts of new users of diclofenac, naproxen, ibuprofen, piroxicam, other NSAIDS, meloxicam, celecoxib, etoricoxib, rofecoxib and valdecoxib. The study period was 1 January 1995 through 2004 (31 March in UK and 28 February in USA). We collected information on covariates including history of upper GI disease, CV disease, hepatic disease, dosage, concomitant medication, and visits to a rheumatologist. We identified 486 076 unique patient-drug pairs in UK and 1 533 239 in USA. In UK population 78 201 (16%) were COX-2 users and in PharMetrics 324 206 (21%) were COX-2 users. Diclofenac and ibuprofen (NSAIDS), and celecoxib and rofecoxib (COX-2) were the agents prescribed most frequently. The duration of therapy was longer among celecoxib and rofecoxib users than among other users. More COX-2 users than NSAIDS users received concomitant gastroprotective agents (GPA), corticosteroids and anti-platelet therapy, and had a history of thromboembolic events and hypertension. PharMetrics patients were prescribed higher doses of NSAIDS and COX-2. The use of any single agent for more than 90 days was uncommon, but more frequent in PharMetrics. Switching was uncommon and was generally to a NSAID. Our results confirm some previous findings from other authors such as the presence of both GI and CV channelling to COX-2 agents but refute others, such as the frequency of drug switching between these agents. The typical use of COX-2 agents in practice is for shorter duration, and at lower doses, than was employed in randomized clinical trials. This difference may help clarify the apparent discrepancy with respect to CV toxicity between the results from

Caffeine: a potential complexing agent for solubility and dissolution enhancement of celecoxib.

PubMed

Shakeel, Faiyaz; Faisal, Mohammed S

2010-01-01

Complexation of caffeine with the drug celecoxib was used to enhance its solubility as well as in vitro dissolution in the present investigation. Caffeine was extracted from tea leaves using the sublimation method. A molecular complex (1:1) of caffeine-celecoxib was prepared using the solubility method. The solubility of celecoxib in distilled water and the caffeine complex was determined using a HPLC method at a wavelength of 250 nm. Dissolution studies of pure celecoxib, a marketed capsule (Celebrex), and the complex were performed using USP dissolution apparatus I for pure celecoxib and the complex and apparatus II for the capsule in distilled water. The highest solubility (48.32 mg/mL) as well as percent dissolution (90.54%) of celecoxib was obtained with the caffeine-celecoxib complex. The results for solubility and dissolution were highly significant as compared to pure celecoxib and the marketed capsule (p < 0.01). These results suggest that caffeine is a promising complexing agent for solubility as well as dissolution enhancement of the poorly soluble drug celecoxib.

Preparation and evaluation of celecoxib-loaded microcapsules with self-microemulsifying core.

PubMed

Homar, Miha; Dreu, Rok; Kerc, Janez; Gasperlin, Mirjana

2009-09-01

The purpose of this study was to prepare alginate microcapsules with a self-microemulsifying system (SMES) containing celecoxib in the core. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to prepare the microcapsules. The encapsulated SMES was shown to increase celecoxib solubility over that of the pure drug more than 400-fold. Microcapsules prepared with a high SMES:celecoxib ratio exhibited distinct core vesicles containing liquid SMES. By modifying the SMES and including an additional chitosan coating, drug loading in the range from 12-40% could be achieved with the degree of encapsulation ranging from 60-82%. Alginate microcapsules loaded with SMES and celecoxib showed increased dissolution rate of celecoxib over that of alginate microcapsules loaded with celecoxib or of the celecoxib alone. Compared to the previous report, drug loading capacity was significantly improved, enabling the formulation of dosage forms which are of suitable size for peroral application.

Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

PubMed

Cho, Kwan Hyung; Jee, Jun-Pil; Yang, Da A; Kim, Sung Tae; Kang, Dongjin; Kim, Dae-Young; Sim, Taeyong; Park, Sang Yeob; Kim, Kyeongsoon; Jang, Dong-Jin

2018-02-01

The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

Mechanism of generation of drug nanocrystals in celecoxib: mannitol nanocrystalline solid dispersion.

PubMed

Bhatt, Varun; Shete, Ganesh; Bansal, Arvind Kumar

2015-11-10

Objective of this work was to understand the mechanism of formation of celecoxib nanocrystals in celecoxib: mannitol nanocrystalline solid dispersion (NSD). Solution of celecoxib and mannitol was spray dried in 1:1 (g:g) proportion to obtain NSD, with average crystallite size of 214.07 ± 45.27 nm. Solubility parameters of celecoxib and mannitol were 23.1 MPa(1/2) and 38.5 MPa(1/2), respectively, hinting their immiscibility. Formation of nanocrystals during NanoCrySP proceeds via intermediate amorphous form of the drug. Earlier work from our lab on hesperetin-mannitol system, had underlined the role of plasticization of amorphous drug by excipient in the formation of nanocrystals. However, in present case, mannitol failed to plasticize amorphous celecoxib and Tg of amorphous celecoxib (56.8°C) showed a negligible change (54.8°C) in presence of mannitol. However, DSC data also suggested crystallization inducing potential of mannitol on amorphous celecoxib. Polarized light microscopy provided evidence that, mannitol facilitated heterogeneous nucleation of amorphous celecoxib at their interface. Transmission electron microscopy analysis suggested that, mannitol acted as a physical barrier to crystal growth of celecoxib crystallites. Thus, though mannitol did not plasticize amorphous celecoxib, it aided in nanocrystal generation by heterogeneous nucleation and providing physical barrier to crystal growth. Copyright © 2015 Elsevier B.V. All rights reserved.

Longitudinal numbers-needed-to-treat (NNT) for achieving various levels of analgesic response and improvement with etoricoxib, naproxen, and placebo in ankylosing spondylitis.

PubMed

Peloso, Paul M; Gammaitoni, Arnold; Smugar, Steven S; Wang, Hongwei; Moore, Andrew R

2011-07-18

Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs. This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation. For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks. For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of NNTs and responder analyses provide

Longitudinal Numbers-Needed-To-Treat (NNT) for Achieving Various Levels of Analgesic Response and Improvement with Etoricoxib, Naproxen, and Placebo in Ankylosing Spondylitis

PubMed Central

2011-01-01

Background Clinical analgesic trials typically report response as group mean results. However, research has shown that few patients are average and most have responses at the extremes. Moreover, group mean results do not convey response levels and thus have limited value in representing the benefit-risk at an individual level. Responder analyses and numbers-needed-to-treat (NNT) are considered more relevant for evaluating treatment response. We evaluated levels of analgesic response and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score improvement and the associated NNTs. Methods This was a post-hoc analysis of a 6-week, randomized, double-blind study (N = 387) comparing etoricoxib 90 mg, etoricoxib 120 mg, naproxen 1000 mg, and placebo in AS. Spine pain and BASDAI were measured on a 100-mm visual analog scale. The number and percentage of patients achieving ≥30% and ≥50% improvement in both BASDAI and spine pain were calculated and used to determine the corresponding NNTs. Patients who discontinued from the study for any reason were assigned zero improvement beyond 7 days of the time of discontinuation. Results For etoricoxib 90 mg, etoricoxib 120 mg and naproxen 1000 mg, the NNTs at 6 weeks compared with placebo were 2.0, 2.0, and 2.7 respectively for BASDAI ≥30% improvement, and 3.2, 2.8, and 4.1 for ≥50% improvement. For spine pain, the NNTs were 1.9, 2.0, and 3.2, respectively, for ≥30% improvement, and 2.7, 2.5, and 3.7 for ≥50% improvement. The differences between etoricoxib and naproxen exceeded the limit of ±0.5 units described as a clinically meaningful difference for pain. Response rates and NNTs were generally similar and stable over 2, 4, and 6 weeks. Conclusions For every 2 patients treated with etoricoxib, 1 achieved a clinically meaningful (≥30%) improvement in spine pain and BASDAI beyond that expected from placebo, whereas the corresponding values were approximately 1 in every 3 patients treated with naproxen. Use of

Celecoxib enhances radiosensitivity of hypoxic glioblastoma cells through endoplasmic reticulum stress

PubMed Central

Suzuki, Kenshi; Gerelchuluun, Ariungerel; Hong, Zhengshan; Sun, Lue; Zenkoh, Junko; Moritake, Takashi; Tsuboi, Koji

2013-01-01

Background Refractoriness of glioblastoma multiforme (GBM) largely depends on its radioresistance. We investigated the radiosensitizing effects of celecoxib on GBM cell lines under both normoxic and hypoxic conditions. Methods Two human GBM cell lines, U87MG and U251MG, and a mouse GBM cell line, GL261, were treated with celecoxib or γ-irradiation either alone or in combination under normoxic and hypoxic conditions. Radiosensitizing effects were analyzed by clonogenic survival assays and cell growth assays and by assessing apoptosis and autophagy. Expression of apoptosis-, autophagy-, and endoplasmic reticulum (ER) stress–related genes was analyzed by immunoblotting. Results Celecoxib significantly enhanced the radiosensitivity of GBM cells under both normoxic and hypoxic conditions. In addition, combined treatment with celecoxib and γ-irradiation induced marked autophagy, particularly in hypoxic cells. The mechanism underlying the radiosensitizing effect of celecoxib was determined to be ER stress loading on GBM cells. Conclusion Celecoxib enhances the radiosensitivity of GBM cells by a mechanism that is different from cyclooxygenase-2 inhibition. Our results indicate that celecoxib may be a promising radiosensitizing drug for clinical use in patients with GBM. PMID:23658321

Randomized trial of switching from prescribed non-selective non-steroidal anti-inflammatory drugs to prescribed celecoxib: the Standard care vs. Celecoxib Outcome Trial (SCOT)

PubMed Central

MacDonald, Thomas M.; Hawkey, Chris J.; Ford, Ian; McMurray, John J.V.; Scheiman, James M.; Hallas, Jesper; Findlay, Evelyn; Grobbee, Diederick E.; Hobbs, F.D. Richard; Ralston, Stuart H.; Reid, David M.; Walters, Matthew R.; Webster, John; Ruschitzka, Frank; Ritchie, Lewis D.; Perez-Gutthann, Susana; Connolly, Eugene; Greenlaw, Nicola; Wilson, Adam; Wei, Li; Mackenzie, Isla S.

2017-01-01

Background Selective cyclooxygenase-2 inhibitors and conventional non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) have been associated with adverse cardiovascular (CV) effects. We compared the CV safety of switching to celecoxib vs. continuing nsNSAID therapy in a European setting. Method Patients aged 60 years and over with osteoarthritis or rheumatoid arthritis, free from established CV disease and taking chronic prescribed nsNSAIDs, were randomized to switch to celecoxib or to continue their previous nsNSAID. The primary endpoint was hospitalization for non-fatal myocardial infarction or other biomarker positive acute coronary syndrome, non-fatal stroke or CV death analysed using a Cox model with a pre-specified non-inferiority limit of 1.4 for the hazard ratio (HR). Results In total, 7297 participants were randomized. During a median 3-year follow-up, fewer subjects than expected developed an on-treatment (OT) primary CV event and the rate was similar for celecoxib, 0.95 per 100 patient-years, and nsNSAIDs, 0.86 per 100 patient-years (HR = 1.12, 95% confidence interval, 0.81–1.55; P = 0.50). Comparable intention-to-treat (ITT) rates were 1.14 per 100 patient-years with celecoxib and 1.10 per 100 patient-years with nsNSAIDs (HR = 1.04; 95% confidence interval, 0.81–1.33; P = 0.75). Pre-specified non-inferiority was achieved in the ITT analysis. The upper bound of the 95% confidence limit for the absolute increase in OT risk associated with celecoxib treatment was two primary events per 1000 patient-years exposure. There were only 15 adjudicated secondary upper gastrointestinal complication endpoints (0.078/100 patient-years on celecoxib vs. 0.053 on nsNSAIDs OT, 0.078 vs. 0.053 ITT). More gastrointestinal serious adverse reactions and haematological adverse reactions were reported on nsNSAIDs than celecoxib, but more patients withdrew from celecoxib than nsNSAIDs (50.9% patients vs. 30.2%; P < 0.0001). Interpretation In

Celecoxib promotes c-FLIP degradation through Akt-independent inhibition of GSK3

PubMed Central

Chen, Shuzhen; Cao, Wei; Yue, Ping; Hao, Chunhai; Khuri, Fadlo R.; Sun, Shi-Yong

2011-01-01

Celecoxib is a COX2 inhibitor that reduces the risk of colon cancer. However, the basis for its cancer chemopreventive activity is not fully understood. In this study, we defined a mechanism of celecoxib action based on degradation of c-FLIP, a major regulator of the death receptor pathway of apoptosis. c-FLIP protein levels are regulated by ubiquitination and proteasome-mediated degradation. We found that celecoxib controlled c-FLIP ubiquitination through Akt-independent inhibition of GSK3 kinase, itself a candidate therapeutic target of interest in colon cancer. Celecoxib increased the levels of phosphorylated GSK3 (p-GSK3), including the α and β forms, even in cell lines where p-Akt levels were not increased. PI3K inhibitors abrogated Akt phosphorylation as expected but had no effect on celecoxib-induced GSK3 phosphorylation. In contrast, PKC inhibitors abolished celecoxib-induced GSK3 phosphorylation, implying that celecoxib influenced GSK3 phosphorylation through a mechanism relied upon PKC but not Akt. GSK3 blockade either by siRNA or kinase inhibitors was sufficient to attenuate c-FLIP levels. Combining celecoxib with GSK3 inhibition enhanced attenuation of c-FLIP and increased apoptosis. Proteasome inhibitor MG132 reversed the effects of GSK3 inhibition and increased c-FLIP ubiquitination, confirming that c-FLIP attenuation was mediated by proteasomal turnover as expected. Our findings reveal a novel mechanism through which the regulatory effects of c-FLIP on death receptor signaling are controlled by GSK3, which celecoxib acts at an upstream level to control independently of Akt. PMID:21868755

Dual function of tributyrin emulsion: solubilization and enhancement of anticancer effect of celecoxib.

PubMed

Kang, Sung Nam; Hong, Soon-Seok; Lee, Mi-Kyung; Lim, Soo-Jeong

2012-05-30

Tributyrin, a triglyceride analogue of butyrate, can act as a prodrug of an anticancer agent butyrate after being cleaved by intracellular enzymes. We recently demonstrated that the emulsion containing tributyrin as an inner oil phase possesses a potent anticancer activity. Herein we sought to develop tributyrin emulsion as a carrier of celecoxib, a poorly-water soluble drug with anticancer activity. Combined treatment of human HCT116 colon cancer cells with free celecoxib plus tributyrin emulsion inhibited the cellular proliferation more effectively than that of each drug alone, suggesting the possibility of tributyrin emulsion as a potential celecoxib carrier. The mean droplet size of emulsions tended to increase as the tributyrin content in emulsion increases and the concentration of celecoxib loaded in emulsions was affected by tributyrin content and the initial amount of celecoxib, but not by the total amount of surfactant mixture. The concentration of celecoxib required to inhibit the growth of HCT116 and B16-F10 cancer cells by 50% was 2.6- and 3.1-fold lowered by loading celecoxib in tributyrin emulsions, compared with free celecoxib. These data suggest that the anticancer activity of celecoxib was enhanced by loading in tributyrin emulsions, probably due to the solubilization capacity and anticancer activity of tributyrin emulsion. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of celecoxib on proliferation and tenocytic differentiation of tendon-derived stem cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Kairui; Zhang, Sheng; Li, Qianqian

Highlights: • Celecoxib has no effects on TDSCs cell proliferation in various concentrations. • Celecoxib reduced mRNAs levels of tendon associated transcription factor. • Celecoxib reduced mRNAs levels of main tendon associated collagen. • Celecoxib reduced mRNAs levels of tendon associated molecules. - Abstract: NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aimsmore » to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 μg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p > 0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 μg/ml) treated group (p < 0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation.« less

Is there any analgesic benefit from preoperative vs. postoperative administration of etoricoxib in total knee arthroplasty under spinal anaesthesia?: A randomised double-blind placebo-controlled trial.

PubMed

Munteanu, Ana Maria; Cionac Florescu, Simona; Anastase, Denisa Madalina; Stoica, Cristian Ioan

2016-11-01

Optimal postoperative analgesia is a challenge for the anaesthesiologist, with the ideal combination of methods, drugs, doses and timing of administration still the subject of research. The COX-2 inhibitors are a class of NSAIDs that may provide useful perioperative analgesia but the optimal timing of administration has not been elucidated. We hypothesised that etoricoxib given 1 h before total knee arthroplasty under spinal anaesthesia will decrease the cumulative dose of intravenous and subcutaneous morphine required to maintain pain intensity of 3 or less on a 10-point numerical rating scale (NRS) during the first postoperative 48 h compared with the same dose of etoricoxib given after surgery. Randomised, double-blind, placebo-controlled trial. University hospital, between January and September, 2014. Overall, 165 patients scheduled for total knee arthroplasty under spinal anaesthesia. The patients were randomised into one of three groups: the ETORICOX-PREOP group received etoricoxib 120 mg orally 1 h before surgery, one placebo pill at the end of surgery and a further 120 mg etoricoxib after 24 h; the ETORICOX-POSTOP group received one placebo pill 1 h before surgery and etoricoxib 120 mg at the end of surgery and after 24 h. The PLACEBO group received one placebo pill 1 h before surgery, one at end of surgery and a third after 24 h. The primary outcome measure was the cumulative dose of intravenous and subcutaneous morphine required during the first postoperative 48 h to maintain a 10-point numerical pain rating scale value of 3 or less. Secondary outcomes measures were duration of analgesia from initiation of spinal anaesthesia until the first analgesic requirement and the side-effects of the treatment. The quantity of morphine over the first postoperative 48 h required by the ETORICOX-PREOP group (44 ± 16 mg) and the ETORICOX-POSTOP group (52 ± 23 mg) were both significantly less than the PLACEBO group (71 ± 20�

PDE5 Inhibitors Enhance Celecoxib Killing in Multiple Tumor Types

PubMed Central

BOOTH, LAURENCE; ROBERTS, JANE L.; CRUICKSHANKS, NICHOLA; TAVALLAI, SEYEDMEHRAD; WEBB, TIMOTHY; SAMUEL, PETER; CONLEY, ADAM; BINION, BRITTANY; YOUNG, HAROLD F.; POKLEPOVIC, ANDREW; SPIEGEL, SARAH; DENT, PAUL

2015-01-01

The present studies determined whether clinically relevant phosphodiesterase 5 (PDE5) inhibitors interacted with a clinically relevant NSAID, celecoxib, to kill tumor cells. Celecoxib and PDE5 inhibitors interacted in a greater than additive fashion to kill multiple tumor cell types. Celecoxib and sildenafil killed ex vivo primary human glioma cells as well as their associated activated microglia. Knock down of PDE5 recapitulated the effects of PDE5 inhibitor treatment; the nitric oxide synthase inhibitor L-NAME suppressed drug combination toxicity. The effects of celecoxib were COX2 independent. Over-expression of c-FLIP-s or knock down of CD95/FADD significantly reduced killing by the drug combination. CD95 activation was dependent on nitric oxide and ceramide signaling. CD95 signaling activated the JNK pathway and inhibition of JNK suppressed cell killing. The drug combination inactivated mTOR and increased the levels of autophagy and knock down of Beclin1 or ATG5 strongly suppressed killing by the drug combination. The drug combination caused an ER stress response; knock down of IRE1α/XBP1 enhanced killing whereas knock down of eIF2α/ATF4/CHOP suppressed killing. Sildenafil and celecoxib treatment suppressed the growth of mammary tumors in vivo. Collectively our data demonstrate that clinically achievable concentrations of celecoxib and sildenafil have the potential to be a new therapeutic approach for cancer. PMID:25303541

Celecoxib promotes c-FLIP degradation through Akt-independent inhibition of GSK3.

PubMed

Chen, Shuzhen; Cao, Wei; Yue, Ping; Hao, Chunhai; Khuri, Fadlo R; Sun, Shi-Yong

2011-10-01

Celecoxib is a COX-2 inhibitor that reduces the risk of colon cancer. However, the basis for its cancer chemopreventive activity is not fully understood. In this study, we defined a mechanism of celecoxib action based on degradation of cellular FLICE-inhibitory protein (c-FLIP), a major regulator of the death receptor pathway of apoptosis. c-FLIP protein levels are regulated by ubiquitination and proteasome-mediated degradation. We found that celecoxib controlled c-FLIP ubiquitination through Akt-independent inhibition of glycogen synthase kinase-3 (GSK3), itself a candidate therapeutic target of interest in colon cancer. Celecoxib increased the levels of phosphorylated GSK3, including the α and β forms, even in cell lines, where phosphorylated Akt levels were not increased. Phosphoinositide 3-kinase inhibitors abrogated Akt phosphorylation as expected but had no effect on celecoxib-induced GSK3 phosphorylation. In contrast, protein kinase C (PKC) inhibitors abolished celecoxib-induced GSK3 phosphorylation, implying that celecoxib influenced GSK3 phosphorylation through a mechanism that relied upon PKC and not Akt. GSK3 blockade either by siRNA or kinase inhibitors was sufficient to attenuate c-FLIP levels. Combining celecoxib with GSK3 inhibition enhanced attenuation of c-FLIP and increased apoptosis. Proteasome inhibitor MG132 reversed the effects of GSK3 inhibition and increased c-FLIP ubiquitination, confirming that c-FLIP attenuation was mediated by proteasomal turnover as expected. Our findings reveal a novel mechanism through which the regulatory effects of c-FLIP on death receptor signaling are controlled by GSK3, which celecoxib acts at an upstream level to control independently of Akt.

Oral versus rectal ibuprofen in healthy volunteers.

PubMed

Vilenchik, Rolanda; Berkovitch, Matitiahu; Jossifoff, Azaria; Ben-Zvi, Zvi; Kozer, Eran

2012-01-01

Ibuprofen is a safe and effective non steroidal anti-inflammatory drug (NSAID). Ibuprofen suppositories are marketed in Europe; but data regarding pharmacokinetics of rectal vs. oral ibuprofen in humans is scarce. The objective of this study is to compare the pharmacokinetics of single-dose rectal vs. oral ibuprofen in healthy adult volunteers. Ten healthy adult male volunteers, aged 20-37 years, received in a non-blind, cross-over setting, two formulations of ibuprofen. First, a 400 mg (about 5 mg/kg) of racemic ibuprofen suppository; second (after a three week washout period) the same dosage of ibuprofen syrup. Blood samples were collected before dosing and for 12 hours after administration. Pharmacokinetics analysis was preformed. Mean peak plasma concentration (Cmax) of rectal ibuprofen was considerably lower, and the mean time to peak (Tmax) considerably longer, compared to oral ibuprofen. Absorption of rectal ibuprofen was considerably lower than oral ibuprofen, with a relative bioequivalence of 63%. Rectal ibuprofen reached therapeutic plasma concentration (>10 µg/ml) 45 minutes after dosing and remained in that range for four hours. The values of Vd/F and CL/F also differ significantly after rectal and oral administration, while no difference was found in the elimination rate constant (Kel) or half-life elimination (t1/2). Racemic ibuprofen suppository has lower bioavailability compared with ibuprofen syrup. Therapeutic plasma concentrations of ibuprofen were reached 45 minutes after dosing and remained in that range for 4 hours. Ibuprofen suppositories can contribute to the management of fever and pain when the oral route is not available.

Localized periorbital edema induced by Ibuprofen.

PubMed

Palungwachira, Piti; Palungwachira, Pranee; Ogawa, Hideoki

2005-12-01

We documented localized periorbital edema in one patient with ibuprofen sensitivity without underlying chronic urticaria. The reaction developed one hour after ingestion of 200 mg of ibuprofen. No systemic symptoms were observed. No other NSAIDs did not induce symptoms. This patient was able to tolerate doses of ibuprofen after pretreatment with terfenadine. These observations suggest that histamine played a central role in this ibuprofen-induced skin reaction. Treatment with terfenadine enabled the patient to tolerate ibuprofen without experiencing any side effects. To the best of our knowledge, this is the first reported case of periorbital edema induced by ibuprofen.

Celecoxib Sensitizes Staphylococcus aureus to Antibiotics in Macrophages by Modulating SIRT1

PubMed Central

Annamanedi, Madhavi; Kalle, Arunasree M.

2014-01-01

We have previously shown that celecoxib in combination with an antibiotic, increase the bacterial sensitivity to antibiotics. However, the underlying molecular mechanism remained elusive. Efficacy of the combinatorial treatment of celecoxib and ampicillin in vitro was evaluated on macrophage-phagocytosed S aureus. To elucidate the mechanism, signaling pathway of infection and inflammation involving TLR2, JNK, SIRT1 and NF-κB was studied by FACS, Western blot, ELISA and activity assays. Combinatorial treatment of ampicillin and celecoxib reduced the bacterial load in the macrophages. Further studies clearly suggested the activation of the master regulator of oxidative stress and inflammation SIRT1,, by celecoxib when used alone and/or in combination with ampicillin. Also, the results indicated that celecoxib inhibited JNK phosphorylation thereby stabilizing and activating SIRT1 protein that inhibited the COX-2 gene transcription with a significant decrease in the levels of protein inflammatory cytokines like IL-6, MIP-1α and IL-1β via inhibition of NF-κB. SIRT1 activation by celecoxib also resulted in increase of catalase and peroxidase activity with a decrease in Nitric oxide levels. In conclusion, we demonstrate a novel role of celecoxib in controlling inflammation as an enhancer of antibiotic activity against bacteria by modulating SIRT1. PMID:24950067

Celecoxib sensitizes Staphylococcus aureus to antibiotics in macrophages by modulating SIRT1.

PubMed

Annamanedi, Madhavi; Kalle, Arunasree M

2014-01-01

We have previously shown that celecoxib in combination with an antibiotic, increase the bacterial sensitivity to antibiotics. However, the underlying molecular mechanism remained elusive. Efficacy of the combinatorial treatment of celecoxib and ampicillin in vitro was evaluated on macrophage-phagocytosed S. aureus. To elucidate the mechanism, signaling pathway of infection and inflammation involving TLR2, JNK, SIRT1 and NF-κB was studied by FACS, Western blot, ELISA and activity assays. Combinatorial treatment of ampicillin and celecoxib reduced the bacterial load in the macrophages. Further studies clearly suggested the activation of the master regulator of oxidative stress and inflammation SIRT1, by celecoxib when used alone and/or in combination with ampicillin. Also, the results indicated that celecoxib inhibited JNK phosphorylation thereby stabilizing and activating SIRT1 protein that inhibited the COX-2 gene transcription with a significant decrease in the levels of protein inflammatory cytokines like IL-6, MIP-1α and IL-1β via inhibition of NF-κB. SIRT1 activation by celecoxib also resulted in increase of catalase and peroxidase activity with a decrease in Nitric oxide levels. In conclusion, we demonstrate a novel role of celecoxib in controlling inflammation as an enhancer of antibiotic activity against bacteria by modulating SIRT1.

Characteristics and molecular basis of celecoxib modulation on Kv7 potassium channels

PubMed Central

Du, XN; Zhang, X; Qi, JL; An, HL; Li, JW; Wan, YM; Fu, Y; Gao, HX; Gao, ZB; Zhan, Y; Zhang, HL

2011-01-01

BACKGROUND AND PURPOSE Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor used for the treatment of pain and inflammation. Emerging and accumulating evidence suggests that celecoxib can affect cellular targets other than COX, such as ion channels. In this study, we characterized the effects of celecoxib on Kv7 K+ channels and compared its effects with the well-established Kv7 channel opener retigabine. EXPERIMENTAL APPROACH A perforated whole-cell patch technique was used to record Kv7currents expressed in HEK 293 cells and M-type currents from rat superior cervical ganglion neurons. KEY RESULTS Celecoxib enhanced Kv7.2–7.4, Kv7.2/7.3 and Kv7.3/7.5 currents but inhibited Kv7.1 and Kv7.1/KCNE1 currents and these effects were concentration dependent. The IC50 value for inhibition of Kv7.1 channels was approximately 4 µM and the EC50 values for activation of Kv7.2–7.4, Kv7.2/Kv7.3 and Kv7.3/Kv7.5 channels were approximately 2–5 µM. The effects of celecoxib were manifested by increasing current amplitudes, shifting the voltage-dependent activation curve in a more negative direction and slowing the deactivation of Kv7 currents. 2,5-Dimethyl-celecoxib, a celecoxib analogue devoid of COX inhibition activity, has similar but greater effects on Kv7currents. Kv7.2(A235T) and Kv7.2(W236L) mutant channels, which have greatly attenuated responses to retigabine, showed a reversed response to celecoxib, from activation to inhibition. CONCLUSIONS AND IMPLICATIONS These results suggest that Kv7 channels are targets of celecoxib action and provide new mechanistic evidence for understanding the effects of celecoxib. They also provide a new approach to developing Kv7 modulators and for studying the structure–function relationship of Kv7 channels. PMID:21564087

Celecoxib interferes to a limited extent with aspirin‐mediated inhibition of platelets aggregation

PubMed Central

Ruzov, Mark; Rimon, Gilad; Pikovsky, Oleg

2015-01-01

Aims The aim of the study was to analyze the interaction between celecoxib and low dose aspirin for COX‐1 binding and its consequences on the aspirin‐mediated antiplatelet effects. Methods We investigated ex vivo the interaction between celecoxib and aspirin for COX‐1 binding and measured the resulting antiplatelet effects. We applied mechanism‐based pharmacokinetic−pharmacodynamic (PKPD) modelling to analyze these data and to predict in vivo platelet aggregation for different doses and administration schedules of aspirin and celecoxib. Results The predictions of the PK‐PD model were consistent with results from previous studies that investigated interaction between aspirin and celecoxib. The modelling results indicate that celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. The extent of this interaction can be substantial (up to 15% increase in platelet aggregation by 200 mg day−1 celecoxib when combined with low dose aspirin) during the first days of aspirin administration in patients who are already treated with celecoxib, and it cannot be prevented by separate administration of the interacting drugs. Conclusions At the recommended therapeutic doses, celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. Patients receiving a combination of low dose aspirin and the recommended doses of celecoxib were not identified to have increased risk of cardiovascular and cerebrovascular events due to competition between these drugs for COX‐1 binding. Interaction between low dose aspirin and other COX‐2 inhibitors and its clinical consequences requires further investigation. PMID:26456703

Development of spray-dried co-precipitate of amorphous celecoxib containing storage and compression stabilizers.

PubMed

Dhumal, Ravindra S; Shimpi, Shamkant L; Paradkar, Anant R

2007-09-01

The purpose of this study was to obtain an amorphous system with minimum unit operations that will prevent recrystallization of amorphous drugs since preparation, during processing (compression) and further storage. Amorphous celecoxib, solid dispersion (SD) of celecoxib with polyvinyl pyrrollidone (PVP) and co-precipitate with PVP and carrageenan (CAR) in different ratios were prepared by the spray drying technique and compressed into tablets. Saturation solubility and dissolution studies were performed to differentiate performance after processing. Differential scanning calorimetry and X-ray powder difraction revealed the amorphous form of celecoxib, whereas infrared spectroscopy revealed hydrogen bonding between celecoxib and PVP. The dissolution profile of the solid dispersion and co-precipitate improved compared to celecoxib and amorphous celecoxib. Amorphous celecoxib was not stable on storage whereas the solid dispersion and co-precipitate powders were stable for 3 months. Tablets of the solid dispersion of celecoxib with PVP and physical mixture with PVP and carrageenan showed better resistance to recrystallization than amorphous celecoxib during compression but recrystallized on storage. However, tablets of co-precipitate with PVP and carageenan showed no evidence of crystallinity during stability studies with comparable dissolution profiles. This extraordinary stability of spray-dried co-precipitate tablets may be attributed to the cushioning action provided by the viscoelastic polymer CAR and hydrogen bonding interaction between celecoxib and PVP. The present study demonstrates the synergistic effect of combining two types of stabilizers, PVP and CAR, on the stability of amorphous drug during compression and storage as compared to their effect when used alone.

Celecoxib: a potent cyclooxygenase-2 inhibitor in cancer prevention.

PubMed

Kismet, Kemal; Akay, M Turan; Abbasoglu, Osman; Ercan, Aygün

2004-01-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely used therapeutic agents in the treatment of pain, inflammation and fever. They may also have a role in the management of cancer prevention, Alzheimer's disease and prophylaxis against cardiovascular disease. These drugs act primarily by inhibiting cyclooxygenase enzyme, which has two isoforms, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Selective COX-2 inhibitors provide potent anti-inflammatory and analgesic effects without the side effects of gastric and renal toxicity and inhibition of platelet function. Celecoxib is a potent COX-2 inhibitor being developed for the treatment of rheumatoid arthritis and osteoarthritis. Chemoprevention is the use of pharmacological or natural agents to prevent, suppress, interrupt or reverse the process of carcinogenesis. For this purpose, celecoxib is being used for different cancer types. The effects of NSAIDs on tumor growth remain unclear, but are most likely to be multifocal. In this article, we reviewed COX-2 selectivity, the pharmacological properties of celecoxib, the use of celecoxib for cancer prevention and the mechanisms of chemoprevention.

Predicting rapid analgesic onset of ibuprofen salts compared with ibuprofen acid: Tlag, Tlow, Tmed, and a novel parameter, TCmaxRef.

PubMed

Miles, Lisa; Hall, Jessica; Jenner, Bartosz; Addis, Richard; Hutchings, Simon

2018-04-27

This study evaluated the early absorption characteristics of ibuprofen salt formulations and standard ibuprofen acid (the reference). In this open-label, crossover, single-center study (NCT02452450) in 32 healthy, fasted adults receiving single oral doses (400 mg ibuprofen) of ibuprofen lysine, ibuprofen liquid capsule, ibuprofen sodium, ibuprofen acid, and paracetamol, intensive blood sampling was conducted for up to 6 h. Time between dosing and the start of absorption (T lag ); a novel parameter, time at which the test formulations (ibuprofen salts) reached the observed maximum plasma concentration (C max ) of the reference (standard ibuprofen acid) (T C maxRef ); and time to achieve therapeutic plasma concentration were measured. Ibuprofen was absorbed more rapidly from the salt formulations than the reference; T lag was 3.3-6.4 min for salt formulations compared with 10.9 min for the reference, and 100% of subjects had a T lag ≤ 5 min for ibuprofen lysine, compared with 61% for ibuprofen liquid capsule, 21% for ibuprofen sodium, and 7% for the reference. T C maxRef was 3.22-5.74-times shorter for salt formulations than for the reference (all p < .0001). The salt formulations reached therapeutic levels earlier than the reference (all p < .0001). All formulations were well tolerated. This study shows that ibuprofen salts are absorbed faster than ibuprofen acid. T lag and T C maxRef demonstrated early start and increased speed of absorption of salts compared with the reference, and may predict more rapid onset of analgesia.

Interaction of celecoxib with membranes: the role of membrane biophysics on its therapeutic and toxic effects.

PubMed

Pereira-Leite, Catarina; Nunes, Cláudia; Lima, José L F C; Reis, Salette; Lúcio, Marlene

2012-11-26

The present work provides a biophysical characterization of the interaction of celecoxib, a cyclo-oxigenase-2 selective nonsteroidal anti-inflammatory drug, with membranes using liposomes, constituted by phosphatidylcholines, as membrane model systems. In order to mimic biological conditions, the experiments were performed at physiological pH (7.4); at an acidic pH to mimic the conditions of the inflamed cells (5.0); and at different membrane physical states (gel, ripple, and fluid phase). Important information regarding the celecoxib-membrane interactions was gathered by the complementary biophysical techniques: derivative spectrophotometry was used to determine liposome/water partition coefficient of celecoxib; dynamic light scattering (DLS) measurements were performed to study the influence of celecoxib on lipid main phase transition temperature; fluorescence binding measurements were made to assess the location of celecoxib within the membrane; and small-angle and wide-angle X-ray scattering (SAXS and WAXS) were used to assess the changes in the structure and order of phosphatidylcholine bilayers caused by the presence of celecoxib. The overall results obtained indicate that celecoxib greatly interacts with membranes. Briefly, celecoxib exhibits a high liposome/water partition coefficient that is non-pH-dependent, but the location of celecoxib within the membrane is pH-dependent. In fact, celecoxib is more deeply located inside the membrane at pH 5.0, while it locates closer to the surface at pH 7.4. DLS, SAXS, and WAXS results have shown a high membrane fluidization in the presence of celecoxib, especially at pH 7.4. Overall, the current study can contribute to a biophysical characterization of the celecoxib-membrane interaction. The relevance of the gathered results will be discussed in terms of the reported celecoxib therapeutic and toxic effects.

Celecoxib-Induced Cytotoxic Effect Is Potentiated by Inhibition of Autophagy in Human Urothelial Carcinoma Cells

PubMed Central

Ho, I-Lin; Chang, Hong-Chiang; Chuang, Yuan-Ting; Lin, Wei-Chou; Lee, Ping-Yi; Chang, Shih-Chen; Chiang, Chih-Kang; Pu, Yeong-Shiau; Chou, Chien-Tso; Hsu, Chen-Hsun; Liu, Shing-Hwa

2013-01-01

Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC) cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum (ER) stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine (3-MA), bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC. PMID:24349176

Celecoxib coupled to dextran via a glutamic acid linker yields a polymeric prodrug suitable for colonic delivery.

PubMed

Lee, Yonghyun; Kim, Jungyun; Kim, Wooseong; Nam, Joon; Jeong, Seongkeun; Lee, Sunyoung; Yoo, Jin-Wook; Kim, Min-Soo; Jung, Yunjin

2015-01-01

Celecoxib, a selective cyclooxygenase-2 inhibitor, is potentially useful for the treatment of colonic diseases such as colorectal cancer and colitis. However, the cardiovascular toxicity of celecoxib limits its routine use in the clinic. Generally, colon-specific delivery of a drug both increases the therapeutic availability in the large intestine and decreases the systemic absorption of the drug, most likely resulting in enhanced therapeutic effects against colonic diseases such as colitis and reduced systemic side effects. To develop a colon-specific prodrug of celecoxib that could reduce its cardiovascular toxicity and improve its therapeutic activity, dextran-glutamic acid-celecoxib conjugate (glutam-1-yl celecoxib-dextran ester [G1CD]) was prepared and evaluated. While stable in pH 1.2 and 6.8 buffer solutions and small-intestinal contents, G1CD efficiently released celecoxib in cecal contents. Oral administration of G1CD to rats delivered a larger amount of celecoxib to the large intestine than free celecoxib. G1CD prevented the systemic absorption of celecoxib and did not decrease the serum level of 6-ketoprostaglandin F1α, an inverse indicator of cardiovascular toxicity of celecoxib. Collectively, G1CD may be a polymeric colon-specific celecoxib prodrug with therapeutic and toxicological advantages.

Physical aspects of dexibuprofen and racemic ibuprofen.

PubMed

Leising, G; Resel, R; Stelzer, F; Tasch, S; Lanziner, A; Hantich, G

1996-12-01

This article presents a comparative study of ibuprofen materials in their solid state. Ibuprofen crystallizes into two different structures for the S(+) enantiomer (dexibuprofen) and racemic ibuprofen. The crystal structure of ibuprofen, its optical absorption and photoluminescence, and the thermodynamic results (melting point and heat of fusion) are discussed. From these physicochemical properties, the authors conclude that dexibuprofen, which is the most active species pharmaceutically, and racemic ibuprofen are inherently different solid-state materials.

Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion

PubMed Central

Shakeel, Faiyaz; Baboota, Sanjula; Ahuja, Alka; Ali, Javed; Shafiq, Sheikh

2008-01-01

Background Celecoxib, a selective cyclo-oxygenase-2 inhibitor has been recommended orally for the treatment of arthritis and osteoarthritis. Long term oral administration of celecoxib produces serious gastrointestinal side effects. It is a highly lipophilic, poorly soluble drug with oral bioavailability of around 40% (Capsule). Therefore the aim of the present investigation was to assess the skin permeation mechanism and bioavailability of celecoxib by transdermally applied nanoemulsion formulation. Optimized oil-in-water nanoemulsion of celecoxib was prepared by the aqueous phase titration method. Skin permeation mechanism of celecoxib from nanoemulsion was evaluated by FTIR spectral analysis, DSC thermogram, activation energy measurement and histopathological examination. The optimized nanoemulsion was subjected to pharmacokinetic (bioavailability) studies on Wistar male rats. Results FTIR spectra and DSC thermogram of skin treated with nanoemulsion indicated that permeation occurred due to the disruption of lipid bilayers by nanoemulsion. The significant decrease in activation energy (2.373 kcal/mol) for celecoxib permeation across rat skin indicated that the stratum corneum lipid bilayers were significantly disrupted (p < 0.05). Photomicrograph of skin sample showed the disruption of lipid bilayers as distinct voids and empty spaces were visible in the epidermal region. The absorption of celecoxib through transdermally applied nanoemulsion and nanoemulsion gel resulted in 3.30 and 2.97 fold increase in bioavailability as compared to oral capsule formulation. Conclusion Results of skin permeation mechanism and pharmacokinetic studies indicated that the nanoemulsions can be successfully used as potential vehicles for enhancement of skin permeation and bioavailability of poorly soluble drugs. PMID:18613981

Safety of preoperative ibuprofen in pediatric tonsillectomy.

PubMed

Michael, Alexander; Buchinsky, Farrel J; Isaacson, Glenn

2018-05-14

Oral ibuprofen is believed to be safe and effective after pediatric adenotonsillectomy. There has been little study of its use as a preoperative analgesic. We attempt to document its safety in this setting. Individual case control study. Children who underwent tonsillectomy or adenotonsillectomy from January 2013 to December 2015 did not receive preoperative ibuprofen. Those who underwent tonsillectomy or adenotonsillectomy from January 2016 to December 2017 received oral ibuprofen 7 mg/kg preoperatively. Pre- and postoperative records were reviewed. Intraoperative bleeding > 50 mL or early postoperative bleeding requiring surgical control were outcome measures. Delayed bleeding events were also recorded. A total of 217 children met inclusion criteria. Of those, 112 patients did not receive preoperative ibuprofen, and 105 patients did receive preoperative ibuprofen. Mean age was 8.7 years (range: 1-18) in the control/non-ibuprofen cohort and 8.3 years (range: 1-18) in the ibuprofen cohort. No child experienced significant intraoperative or early postoperative bleeding in the non-ibuprofen (95% confidence interval [CI] 0-0.027) or in the ibuprofen cohort (95% CI 0- 0.029). Delayed bleeding rates were similar in both groups. In this series, children treated with preoperative ibuprofen did not experience increased bleeding during or soon after tonsillectomy compared to controls. Pain control was not studied in these patients. These favorable safety data argue for a future prospective randomized study of preoperative ibuprofen's effectiveness in reducing pain and opioid requirement after pediatric tonsillectomy. 3B. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

The Effect of Gabapentin Plus Celecoxib on Pain and Associated Complications After Laminectomy.

PubMed

Vasigh, Aminolah; Jaafarpour, Molouk; Khajavikhan, Javaher; Khani, Ali

2016-03-01

Prevention and treatment of postoperative pain is a major challenge in postoperative care and well-being of the surgical patient. The multimodal analgesic method has been recommended as an alternative treatment for the management of postoperative pain. To assess the comparative effect of gabapentin versus gabapentin plus celecoxib on pain and associated complications after laminectomy. In this randomized double- blind clinical trial, 114 patients scheduled for elective laminectomy received gabapentin (n=38, 900 mg daily), gabapentin plus celecoxib (n=38, 200 mg celecoxib plus 300mg gabapentin twice a day), and placebo (n=38, capsule containing starch). Visual Analog Scale (VAS) was used to determine the severity of pain. Complications after surgery, anxiety scores before surgery and patient's satisfaction 24 hour after surgery were recorded. The mean pain sevenity score and morphine consumption in the gabapentin plus celecoxib group were less compared to the placebo and gabapentin group respectively at various intervals (p < 0.001). The mean anxiety score, shivering, nausea, vomiting and pruritus in the gabapentin group were significantly lower compared to the placebo and gabapentin plus celecoxib groups respectively (p < 0.001, p < 0.05). The frequencies of drowsiness (42.1%) in the gabapentin group were significantly high compared to the placebo and gabapentin plus celecoxib group respectively (p <0.001, p< 0.05). In the gabapentin plus celecoxib group patient satisfaction was significantly higher compared to the placebo and gabapentin group (p< 0.05). Combination of 300 mg gabapentin plus 200 mg celecoxib twice a day is a good alternative in multimodal analgesia, effective in pain control with lesser side effects seen with gabapentin alone.

Ibuprofen

MedlinePlus

... be giving cough and cold medications to a child.Nonprescription cough and cold combination products, including products ... a combination product that contains ibuprofen to a child, read the package label carefully to be sure ...

Use of celecoxib correlates with increased relative risk of acute pancreatitis: a case-control study in Taiwan.

PubMed

Hung, Shih-Chang; Hung, Shih-Rong; Lin, Cheng-Li; Lai, Shih-Wei; Hung, Hung-Chang

2015-10-01

This study evaluated whether there is an association between the use of celecoxib and acute pancreatitis in Taiwan. We conducted a case-control study using the database of the Taiwan National Health Insurance Program. The participants comprised 5,095 subjects, aged 20-84 years, with a first admission episode of acute pancreatitis from 2000 to 2011 as the cases and 20,380 randomly selected sex-matched and age-matched subjects without acute pancreatitis as the controls. The absence of celecoxib prescription was defined as "never used." Current use of celecoxib was defined as subjects who had received at least one prescription for celecoxib within 3 days before diagnosis with acute pancreatitis. A multivariate unconditional logistic regression model was used to calculate the odds ratio (OR) and 95% confidence interval (CI) for acute pancreatitis associated with the use of celecoxib. Compared with subjects who never used celecoxib, the adjusted OR of acute pancreatitis was 5.62 in subjects with current use of celecoxib (95% CI=3.33-9.46). The current use of celecoxib is associated with an increased risk of acute pancreatitis.

Sensitivity of single-domain versus multiple-domain outcome measures to identify responders in chronic low-back pain: pooled analysis of 2 placebo-controlled trials of etoricoxib.

PubMed

Jensen, Mark P; Schnitzer, Thomas J; Wang, Hongwei; Smugar, Steven S; Peloso, Paul M; Gammaitoni, Arnold

2012-01-01

A composite responder index for chronic low-back pain (CLBP) has recently been proposed to evaluate the efficacy of CLBP treatments in clinical trials. We compared the responsiveness of this composite measure with a number of single-item responder definitions. We pooled data from 2 placebo-controlled studies of etoricoxib in CLBP to evaluate 5 response criteria: 30% pain intensity (PI) reduction; 50% PI reduction; 20 mm absolute reduction (100 mm PI visual analog scale); patient global assessment of response to therapy (PGART); and the composite criteria of 30% reduction in PI+30% improvement in PGART of disease status+no worsening in function. We used bootstrap analysis and logistic regression to assess the ability to differentiate etoricoxib and placebo, and the κ coefficient to assess agreement among the responder criteria. The criterion of a 20 mm improvement in PI resulted in the greatest proportion (71.5%) of patients being classified as responders and all criteria separated etoricoxib from placebo (P≤0.0001). PGART had the highest discriminant ability (odds ratio 5.90), and was significantly (P<0.05) more discriminant than the 20 mm and ≥30% improvements and the composite criteria. After adjusting for all other measures, only PGART continued to show a significant treatment effect for etoricoxib versus placebo (P=0.0003). Kappa values contrasting the composite criteria and the single-item measures ranged from 0.59 to 0.85. These findings do not support the superiority of a composite index over single-item ratings of PI and PGART ratings, but do suggest that PGART ratings may be more responsive to treatment, perhaps because they measure something in addition to change in PI.

Perioperative pharmacokinetics of ibuprofen enantiomers after rectal administration.

PubMed

Kyllönen, Matti; Olkkola, Klaus T; Seppälä, Timo; Ryhänen, Pauli

2005-07-01

Ibuprofen is a nonsteroidal anti-inflammatory drug which has both peripheral and central analgesic effects. Ibuprofen has been shown to be an effective antipyretic and postoperative analgesic drug both in adults and children with few side effects. Pharmacokinetics of rectal ibuprofen has not been studied, although suppositories are frequently used for perioperative pain control in children. There were four study groups: full-term infants aged 1-7 weeks (n = 9), infants aged 8-25 weeks (n = 8), and infants aged 26-52 weeks (n = 7). Adult patients were 20-40 years old (n = 7). Ibuprofen suppository 20 mg.kg(-1) was administered after induction of anesthesia. Blood samples were collected from 20 min to 10 h after dosing and pharmacokinetic analysis of ibuprofen enantiomers were done. Both ibuprofen enantiomers were detectable in blood in 20 min. Total ibuprofen plasma concentrations >10 mg.l(-1) were seen from 40 min to 8 h. Values for T(max) of ibuprofen enantiomers and total ibuprofen were higher in the adult group than any of the infant groups (P < 0.05). In addition, values for physiological (standardized) t(1/2) of (R)-(-)- and (S)-(+)-ibuprofen were higher in infants aged 1-7 weeks than the adults (P < 0.05). None of the other pharmacokinetic variables, C(max), AUC, chronological t(1/2) or AUC ratio differed between the groups. A single dose of ibuprofen suppository 20 mg.kg(-1) after induction of anesthesia guarantees analgesic plasma concentrations during the early postoperative period. Except for the delayed absorption of ibuprofen in adults and higher physiological t(1/2) in infants aged 1-7 weeks, no major pharmacokinetic differences were observed between study groups.

Reappraisal of the Therapeutic Role of Celecoxib in Cholangiocarcinoma

PubMed Central

Juang, Horng-Heng; S. Pang, Jong-Hwei; Yu, Chung-Shan; Lin, Kun-Ju; Yeh, Ta-Sen; Jan, Yi-Yin

2013-01-01

Cholangiocarcinoma (CCA), a lethal disease, affects many thousands worldwide yearly. Surgical resection provides the best chance for a cure; however, only one-third of CCA patients present with a resectable tumour at the time of diagnosis. Currently, no effective chemotherapy is available for advanced CCA. Cyclooxygenase-2 (COX-2) is a potential oncogene expressing in human CCA tissues and represents a candidate target for treatment; however, COX-2 inhibitors increase the risk of negative cardiovascular events as application for chemoprevention aim. Here, we re-evaluated the effectiveness and safety of celecoxib, one widely used COX-2 inhibitor, in treating CCA. We demonstrated that celecoxib exhibited an anti-proliferative effect on CGCCA cells via cell cycle arrest at G2 phase and apoptosis induction. Treatment for 5 weeks high dose celecoxib (160 mg/kg) significantly repressed thioacetamide-induced CCA tumour growth in rats as monitored by animal positron emission tomography through apoptosis induction. No obviously observable side effects were noted during the therapeutic period. As retrospectively reviewing 78 intrahepatic mass-forming CCA patients, their survival was strongly and negatively associated with a positive resection margin and high COX-2 expression. Based on our result, we concluded that short-term high dose celecoxib may be a promising therapeutic regimen for CCA. Yet its clinical application still needs more studies to prove its safety. PMID:23922859

Celecoxib:Nicotinamide Dissociation: Using Excipients to Capture the Cocrystal's Potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Remenar,J.; Peterson, M.; Stephens, P.

2007-01-01

The cocrystal of celecoxib and nicotinamide (Cel:Nic) was crystallized from chloroform in a 1:1 ratio, and the structure has been solved from powder X-ray diffraction data. The dissolution and solubility of Cel:Nic are medium dependent and can be attributed to differences in conversion of Cel:Nic to celecoxib polymorphs I and III (Cel-I and Cel-III). The presence of low concentrations of surfactants facilitates the rapid conversion of neat Cel:Nic to large aggregates of Cel-III that dissolve more slowly than commercial Cel-III into 1% SDS solution. In contrast, combinations of Cel:Nic with both 1-10% solid SDS and PVP wet rapidly and convertmore » to a mixture of amorphous celecoxib and a micron-sized crystalline celecoxib form IV (Cel-IV), which has recently been shown to be up to 4-fold more bioavailable than marketed Cel-III. More than 90% of the suspended material dissolves within 2 min at 37 C when transferred to 1% SDS solution. This example highlights the importance of exploring the form conversion of cocrystals in aqueous media prior to pharmacokinetic studies, and illustrates the potential of simple formulations to overcome the limitations caused by rapid dissociation of cocrystals and recrystallization of poorly soluble forms in aqueous media.« less

Celecoxib: Nicotinamide Dissociateion: Using Excipients to Capture the Cocrystal's Potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Remenar,J.; Peterson, M.; Stephens, P.

2007-01-01

The cocrystal of celecoxib and nicotinamide (Cel:Nic) was crystallized from chloroform in a 1:1 ratio, and the structure has been solved from powder X-ray diffraction data. The dissolution and solubility of Cel:Nic are medium dependent and can be attributed to differences in conversion of Cel:Nic to celecoxib polymorphs I and III (Cel-I and Cel-III). The presence of low concentrations of surfactants facilitates the rapid conversion of neat Cel:Nic to large aggregates of Cel-III that dissolve more slowly than commercial Cel-III into 1% SDS solution. In contrast, combinations of Cel:Nic with both 1-10% solid SDS and PVP wet rapidly and convertmore » to a mixture of amorphous celecoxib and a micron-sized crystalline celecoxib form IV (Cel-IV), which has recently been shown to be up to 4-fold more bioavailable than marketed Cel-III. More than 90% of the suspended material dissolves within 2 min at 37 C when transferred to 1% SDS solution. This example highlights the importance of exploring the form conversion of cocrystals in aqueous media prior to pharmacokinetic studies, and illustrates the potential of simple formulations to overcome the limitations caused by rapid dissociation of cocrystals and recrystallization of poorly soluble forms in aqueous media.« less

Update on ibuprofen for rheumatoid arthritis.

PubMed

Ward, J R

1984-07-13

In doses of 1,200 mg/day or more, ibuprofen is as effective as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of rheumatoid arthritis. The tolerability and safety of ibuprofen are superior to those of aspirin and compare favorably with those of other NSAIDs. Although additional controlled trials are indicated to determine optimal dose, ibuprofen's excellent therapeutic index establishes it as a useful drug in the treatment of rheumatoid arthritis.

Polyuria, acidosis, and coma following massive ibuprofen ingestion.

PubMed

Levine, Michael; Khurana, Amandeep; Ruha, Anne-Michelle

2010-09-01

Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose is rare. We report a case of a massive ibuprofen ingestion who developed polyuria, acidosis, and coma but survived, despite having a serum ibuprofen concentration greater than previous fatal cases. A 19-year-old man ingested 90 g (1,200 mg/kg) ibuprofen. He was initially awake and alert, but his level of consciousness deteriorated over several hours. Seven hours following the ingestion, he was intubated and mechanically ventilated secondary to loss of airway reflexes. He developed a lactic acidosis and polyuria, which lasted for nearly 24 h. His serum creatinine peaked at 1.12 mg/dL. An ibuprofen level drawn 7 h postingestion was 739.2 mg/L (therapeutic 5-49 mg/L). We describe a case of a massive ibuprofen overdose characterized by metabolic acidosis, coma, and a state of high urine output who survived with aggressive supportive care. This case is unique in several ways. First, ibuprofen levels this high have only rarely been described. Second, polyuria is very poorly described following ibuprofen ingestions.

The ErbB family and androgen receptor signaling are targets of Celecoxib in prostate cancer.

PubMed

Brizzolara, Antonella; Benelli, Roberto; Venè, Roberta; Barboro, Paola; Poggi, Alessandro; Tosetti, Francesca; Ferrari, Nicoletta

2017-08-01

Inflammation plays a central role in prostate cancer (PCa) development through significant crosstalk between the COX-2-ErbB family receptor network and androgen receptor (AR)-EGFR signaling pathways. The purpose of this work was to determine the ability of the COX-2 inhibitor Celecoxib to modulate the EGFR-AR signaling pathway in androgen-dependent PCa cells and to provide a rationale for its beneficial use in chemopreventive strategies. Functional studies of Celecoxib activity were performed on LNCaP prostate cancer cells. Western blotting, gene expression analysis, dual-luciferase reporter assay and ELISA were applied to assess the Celecoxib mechanisms of action. We found that Celecoxib, through EGF and amphiregulin (AREG) induction, caused EGFR and ErbB2 activation and consequent degradation associated with the inhibition of androgenic signaling. By upregulating the E3 ubiquitin ligase Nrdp1, Celecoxib also efficiently downregulated ErbB3, which is strongly implicated in castration-resistant prostate cancer. Lastly, Celecoxib directly regulated AR transcription and translation independent of ErbB activation by downregulating the RNA binding protein heterogeneous nuclear ribonucleoprotein K (hnRNP K). The simultaneous suppression of ErbB kinases and androgen signaling by Celecoxib represents a novel strategy to interrupt the vicious cycle of AR/ErbB cross-talk with the primary purpose of undermining their resilient signaling in prostate cancer progression. Our data provide important premises for the chemopreventive use of Celecoxib in the clinical management of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Antitumor effect of the selective COX-2 inhibitor celecoxib on endometrial adenocarcinoma in vitro and in vivo

PubMed Central

XIAO, YITAO; TENG, YINCHENG; ZHANG, RUI; LUO, LAIMIN

2012-01-01

The aim of this study was to investigate the antitumor effect of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib on endometrial adenocarcinoma in mice. Various amounts of celecoxib were added to HEC-1B cells in vitro for different durations. Cell cycle and apoptosis were analyzed using flow cytometry. HEC-1B cytostasis, invasiveness and COX-2 expression were examined by MTT, transwell cabin and western blot assays, respectively. An in vivo human endometrial adenocarcinoma model was established in BALB/c nude mice using HEC-1B cells. For two weeks, the celecoxib groups were treated with celecoxib 2 or 4 mg/day via oral administration and the control group was treated with saline. Tumor volume, growth curves and the inhibition rate (IR) were recorded. COX-2 expression levels and microvessel density (MVD) were investigated using an immunohistochemical technique. In the celecoxib groups, cell proliferation was significantly inhibited in a concentration- and time-dependent manner. The proportion of cells in the G0/G1 phase increased within 24 h after the addition of celecoxib whereas those in the S and G2/M phases decreased with an increasing apoptosis peak (sub-G1) and apoptosis rate. The microporous Matrigel-coated polycarbonate membrane of the Transwell cabin was traversable for the HEC-1B cells. The invasiveness was attenuated when the celecoxib concentration was increased. The tumor growth was also greatly inhibited when the celecoxib concentration was increased. The tumor IRs were 32.4 and 48.6% following treatment with 2 and 4 mg/day celecoxib, respectively. COX-2 was mainly expressed in the cytoplasm of the tumor cells. In the celecoxib groups, the COX-2 expression levels were concentration-dependent. The COX-2 expression level and MVD decreased when the celecoxib concentration was increased. The results of dependability analysis revealed that the COX-2 expression level was positively correlated with MVD (r=0.921; P<0.01). The antitumor effect of

Celecoxib extends C. elegans lifespan via inhibition of insulin-like signaling but not cyclooxygenase-2 activity

PubMed Central

Ching, Tsui-Ting; Chiang, Wei-Chung; Chen, Ching-Shih; Hsu, Ao-Lin

2011-01-01

Summary One goal of aging research is to develop interventions that combat age-related illnesses and slow aging. Although numerous mutations have been shown to achieve this in various model organisms, only a handful of chemicals have been identified to slow aging. Here we report that celecoxib, a non-steroidal anti-inflammatory drug (NSAID) widely used to treat pain and inflammation, extends C. elegans lifespan and delays the age-associated physiological changes, such as motor activity declines. Celecoxib also delays the progression of age-related proteotoxicity as well as tumor growth in C. elegans. Celecoxib was originally developed as a potent COX-2 inhibitor. However, the result from a structural-activity analysis demonstrated that the anti-aging effect of celecoxib might be independent of its COX-2 inhibitory activity, as analogs of celecoxib that lack cyclooxygenase-2 (COX-2) inhibitory activity produces a similar effect on lifespan. Furthermore, we found that celecoxib acts directly on 3’-phosphoinositide-dependent kinase-1 (PDK-1), a component of the insulin/IGF-1 signaling (IIS) cascade to increase lifespan. PMID:21348927

Evening primrose oil or forskolin ameliorates celecoxib-enhanced upregulation of tissue factor expression in mice subjected to lipopolysaccharide-induced endotoxemia.

PubMed

Mosaad, Sarah M; Zaitone, Sawsan A; Ahmed, Amal A M; Abo-Elmatty, Dina M; El-Baz, Amani A; Moustafa, Yasser M

2017-05-01

Celecoxib, a selective cyclooxygenase-2 inhibitor, produces thrombotic events in patients predisposed to cardiovascular risk factors. One theory reported an increase in endothelial expression of tissue factor (TF) as a predisposing factor. This work explored the effect of evening primrose oil (EPO), a source of prostaglandin E1, and forskolin (a cyclic adenosine monophosphate stimulator) against the prothrombotic effect of celecoxib in mice. Lipopolysaccharide mouse model of endotoxemia was used to induce an upregulation of TF activity. Male mice received celecoxib (25 mg/kg), celecoxib plus EPO, or celecoxib plus forskolin for 4 weeks and then subjected to a prothrombotic challenge in the form of an intraperitoneal injection of lipopolysaccharide. Results showed an increase in plasma TF activity, endothelial TF expression, and thrombin-antithrombin (TAT) but lower antithrombin III (ATIII) level in mice that received celecoxib in comparison to those that received the vehicle. Adding EPO or forskolin to celecoxib regimen significantly decreased the prothrombotic effect of celecoxib. A positive correlation (r = 0.8501) was found between TF activity and TAT. Co-administration of EPO or forskolin decreased the activity of TF and mitigated the prothrombotic effect of celecoxib. Therefore, these combinations may have the utility to abrogate the prothrombotic adverse effect of celecoxib in clinical setting.

Celecoxib Versus Placebo in Tonsillectomy: A Prospective, Randomized, Double-Blind Placebo-Controlled Trial.

PubMed

Van Daele, Douglas J; Bodeker, Kellie L; Trask, Douglas K

2016-10-01

Celecoxib is a cyclooxygenase-2-specific inhibitor indicated to treat acute pain and pain secondary to osteoarthritis and rheumatoid arthritis. Surgical models of acute pain have demonstrated superior pain relief to placebo. The objective of this study was to test the safety and efficacy of celecoxib for pain relief after tonsillectomy compared to placebo. Adult subjects were randomized to 200 mg celecoxib versus placebo with a loading dose the night before surgery then twice daily for 10 days. Subjects were instructed to supplement the study drug with hydrocodone/acetaminophen liquid or acetaminophen for pain as needed. Subjects completed a daily diary regarding their pain, nausea, vomiting, diet, and activity. Seventeen subjects enrolled. Intraoperative blood loss was similar between groups, and no subject had postoperative bleeding. Three patients returned to the emergency department for treatment, and 2 patients could not complete the diaries, all in the placebo group. Subjects in the placebo group required statistically significant (P < .05) higher doses of narcotic and acetaminophen to control pain. Pain and diet rating scores were slightly better in the celecoxib group compared to placebo. In this small cohort, celecoxib reduced postoperative narcotic and acetaminophen requirements compared to placebo without complications. © The Author(s) 2016.

Down-Regulation of Glucose-Regulated Protein (GRP) 78 Potentiates Cytotoxic Effect of Celecoxib in Human Urothelial Carcinoma Cells

PubMed Central

Huang, Kuo-How; Kuo, Kuan-Lin; Chen, Shyh-Chyan; Weng, Te-I; Chuang, Yuan-Ting; Tsai, Yu-Chieh; Pu, Yeong-Shiau; Chiang, Chih-Kang; Liu, Shing-Hwa

2012-01-01

Celecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor that has been reported to elicit anti-proliferative response in various tumors. In this study, we aim to investigate the antitumor effect of celecoxib on urothelial carcinoma (UC) cells and the role endoplasmic reticulum (ER) stress plays in celecoxib-induced cytotoxicity. The cytotoxic effects were measured by MTT assay and flow cytometry. The cell cycle progression and ER stress-associated molecules were examined by Western blot and flow cytometry. Moreover, the cytotoxic effects of celecoxib combined with glucose-regulated protein (GRP) 78 knockdown (siRNA), (−)-epigallocatechin gallate (EGCG) or MG132 were assessed. We demonstrated that celecoxib markedly reduces the cell viability and causes apoptosis in human UC cells through cell cycle G1 arrest. Celecoxib possessed the ability to activate ER stress-related chaperones (IRE-1α and GRP78), caspase-4, and CCAAT/enhancer binding protein homologous protein (CHOP), which were involved in UC cell apoptosis. Down-regulation of GRP78 by siRNA, co-treatment with EGCG (a GRP78 inhibitor) or with MG132 (a proteasome inhibitor) could enhance celecoxib-induced apoptosis. We concluded that celecoxib induces cell cycle G1 arrest, ER stress, and eventually apoptosis in human UC cells. The down-regulation of ER chaperone GRP78 by siRNA, EGCG, or proteosome inhibitor potentiated the cytotoxicity of celecoxib in UC cells. These findings provide a new treatment strategy against UC. PMID:22438966

Status of etoricoxib in the treatment of rheumatic diseases. Expert panel opinion

PubMed Central

Majdan, Maria; Mastalerz-Migas, Agnieszka; Niewada, Maciej; Skrzydło-Radomańska, Barbara; Mamcarz, Artur

2017-01-01

Pain is one of the most disabling symptoms of rheumatoid diseases. Patients with pain secondary to osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS) or gout require effective analgesic treatment, and the physician’s task is to select a drug that is best suited for an individual patient. The choice of pharmacotherapy should be based both on drug potency and clinical efficacy, and its safety profile, particularly in the elderly population, as the number of comorbidities (and hence the risk of treatment complications and drug interactions) rises with age. In cases involving a high risk of gastrointestinal complications or concerns about hepatotoxicity, with a low cardiovascular risk, the first-line nonsteroidal anti-inflammatory drugs to consider should be coxibs including etoricoxib. PMID:29491537

Effect of Formulation Variables on Preparation of Celecoxib Loaded Polylactide-Co-Glycolide Nanoparticles

PubMed Central

Cooper, Dustin L.; Harirforoosh, Sam

2014-01-01

Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v), drug amount (5, 10, 15, and 20 mg), and emulsifier (lecithin) on nanoparticle characterization were examined for formula optimization. The use of 0.1, 0.25, and 0.5% w/v didodecyldimethylammonium bromide resulted in a more than 5-fold increase in zeta potential and a more than 1.5-fold increase in entrapment efficiency with a reduction in particle size over 35%, when compared to stabilizer free formulation. Nanoparticle formulations were also highly influenced by emulsifier and drug amount. Using 0.25% w/v didodecyldimethylammonium bromide NP formulations, peak zeta potential was achieved using 15 mg celecoxib with emulsifier (17.15±0.36 mV) and 20 mg celecoxib without emulsifier (25.00±0.18 mV). Peak NP size reduction and entrapment efficiency was achieved using 5 mg celecoxib formulations with (70.87±1.24 nm and 95.55±0.66%, respectively) and without (92.97±0.51 nm and 95.93±0.27%, respectively) emulsifier. In conclusion, formulations using 5 mg celecoxib with 0.25% w/v didodecyldimethylammonium bromide concentrations produced nanoparticles exhibiting enhanced size reduction and entrapment efficiency. Furthermore, emulsifier free formulations demonstrated improved zeta potential when compared to formulations containing emulsifier (p<0.01). Therefore, our results suggest the use of emulsifier

Determination of Solubility Parameters of Ibuprofen and Ibuprofen Lysinate.

PubMed

Kitak, Teja; Dumičić, Aleksandra; Planinšek, Odon; Šibanc, Rok; Srčič, Stanko

2015-12-03

In recent years there has been a growing interest in formulating solid dispersions, which purposes mainly include solubility enhancement, sustained drug release and taste masking. The most notable problem by these dispersions is drug-carrier (in)solubility. Here we focus on solubility parameters as a tool for predicting the solubility of a drug in certain carriers. Solubility parameters were determined in two different ways: solely by using calculation methods, and by experimental approaches. Six different calculation methods were applied in order to calculate the solubility parameters of the drug ibuprofen and several excipients. However, we were not able to do so in the case of ibuprofen lysinate, as calculation models for salts are still not defined. Therefore, the extended Hansen's approach and inverse gas chromatography (IGC) were used for evaluating of solubility parameters for ibuprofen lysinate. The obtained values of the total solubility parameter did not differ much between the two methods: by the extended Hansen's approach it was δt = 31.15 MPa(0.5) and with IGC it was δt = 35.17 MPa(0.5). However, the values of partial solubility parameters, i.e., δd, δp and δh, did differ from each other, what might be due to the complex behaviour of a salt in the presence of various solvents.

An apple oligogalactan potentiates the growth inhibitory effect of celecoxib on colorectal cancer.

PubMed

Li, Yuhua; Niu, Yinbo; Sun, Yang; Mei, Lin; Zhang, Bangle; Li, Qian; Liu, Li; Zhang, Rong; Chen, Jianfa; Mei, Qibing

2014-01-01

Multiple studies have indicated that selective cyclooxygenase-2 (COX-2) inhibitors possess clinically chemopreventive and preclinically anticancer activities. Their long-term use, however, may be limited by the cardiovascular toxicity. This study tried to investigate whether an apple oligogalactan (AOG) could enhance the growth inhibitory effect of celecoxib on colorectal cancer. Caco-2 and HT-29 cell lines were exposed to different concentrations of AOG (0-1 g/L), celecoxib (0-25 μmol/L), and their combination. COX-2 levels were assessed by reverse transcription PCR and Western blot. COX-2 activity was evaluated by measuring prostaglandin E2 concentration. A colitis-associated colorectal cancer (CACC) mouse model was used to determine the effect of the combination in vivo. AOG (0.1-0.5 g/L) could potentiate the inhibitory effect of physiologic doses of celecoxib (5 μmol/L) on cell growth and decrease COX-2 expressions both at RNA and protein levels. In vivo, the combination (2.5% AOG plus 0.04% celecoxib, w/w) prevented against CACC in mice effectively. Our data indicate that AOG could potentiate the growth inhibitory effect of celecoxib on colorectal cancer both in vitro and in vivo through influencing the expression and function of COX-2 and phosphorylation of MAPKs, which suggests a new possible combinatorial strategy in colorectal cancer therapy.

Celecoxib plus chemoradiotherapy for locally advanced rectal cancer: a phase II TCOG study.

PubMed

Wang, Ling-Wei; Hsiao, Chin-Fu; Chen, William Tzu-Liang; Lee, Hao-Hsien; Lin, Tzu-Chen; Chen, Hung-Chang; Chen, Hong-Hwa; Chien, Chun-Ru; Lin, Tze-Yi; Liu, Tsang-Wu

2014-05-01

To report the results of a phase II trial combining celecoxib and preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Patients with clinical stage II or III rectal cancer were treated with radiotherapy of 44 Gy in 22 fractions. Concurrent chemotherapy consisted of oral tegafur-uracil and folinate on days 1-30 and 38-65. Celecoxib (400 mg/day) given from days 1 to 65. Surgery was done on day 70. The expression of cyclooxygenase 2 (COX-2) in tumor tissues was evaluated microscopically as a prognostic factor. From 2008 to 2011, 53 patients completed CRT+ celecoxib therapy and 47 received radical surgery. Grade 3 diarrhea developed in 5 (9%). Grade 4 anemia was seen in 2 (4%). Pathological complete response (pCR) was seen in 6 (13%). T or N downstaging found in 38 (81%). Sphincter preservation was achieved in 77% of low-positioned tumors. Patients with tumors expressing high-level COX-2 after CRT + celecoxib treatment had inferior pelvic control (P = 0.01), disease-free survival (P = 0.04), and overall survival (P = 0.03) than those with low-level expression. Celecoxib can be safely combined with preoperative CRT for rectal cancer. More intensified adjuvant therapy may be considered for tumors expressing high-level COX-2 after CRT and surgery. © 2013 Wiley Periodicals, Inc.

Celecoxib suppresses fibroblast growth factor-2 expression in pancreatic ductal adenocarcinoma PANC-1 cells.

PubMed

Li, Jing; Luo, Miaosha; Wang, Yan; Shang, Boxin; Dong, Lei

2016-09-01

The inhibition of cyclooxygenase (COX)-2 has been reported to suppress growth and induce apoptosis in human pancreatic cancer cells. Nevertheless, the precise biological mechanism of how celecoxib, a selective COX-2 inhibitor, regulates the growth and invasion of pancreatic tumors is not completely understood. It has been shown that fibroblast growth factor-2 (FGF-2) and its receptor levels correlate with the inhibition of cancer cell proliferation, migration and invasion in pancreatic ductal adenocarcinoma (PDAC). Therefore, the aim of the present study was to examine the hypothesis that the antitumor activity of celecoxib in PDAC may be exerted through modulation of FGF-2 function. In the present study, we evaluated the effects of celecoxib on the proliferation, migration, invasion and apoptosis of the PANC-1 cell line. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were used to examine the expression of FGF-2, FGFR-2, ERK1/2 and MMPs. In the present study, FGF-2 and FGFR-2 were expressed in PANC-1 cells and FGF-2 exerted a stimulatory effect on phosphorylated extracellular signal regulated kinase (p-ERK) expression. Celecoxib treatment suppressed FGF-2 and FGFR-2 expression and decreased MMP-2, MMP-9 and p-ERK expression in the PANC-1 cells. Furthermore, celecoxib treatment caused the resistance of PANC-1 cells to FGF-2 induced proliferation, migration and invasion ability, as well as the increase in their apoptotic rate. Our data provide evidence that targeting FGF-2 with celecoxib may be used as an effective treatment in PDAC.

Influence of ibuprofen on phospholipid membranes

NASA Astrophysics Data System (ADS)

Jaksch, Sebastian; Lipfert, Frederik; Koutsioubas, Alexandros; Mattauch, Stefan; Holderer, Olaf; Ivanova, Oxana; Frielinghaus, Henrich; Hertrich, Samira; Fischer, Stefan F.; Nickel, Bert

2015-02-01

A basic understanding of biological membranes is of paramount importance as these membranes comprise the very building blocks of life itself. Cells depend in their function on a range of properties of the membrane, which are important for the stability and function of the cell, information and nutrient transport, waste disposal, and finally the admission of drugs into the cell and also the deflection of bacteria and viruses. We have investigated the influence of ibuprofen on the structure and dynamics of L-α -phosphatidylcholine (SoyPC) membranes by means of grazing incidence small-angle neutron scattering, neutron reflectometry, and grazing incidence neutron spin echo spectroscopy. From the results of these experiments, we were able to determine that ibuprofen induces a two-step structuring behavior in the SoyPC films, where the structure evolves from the purely lamellar phase for pure SoyPC over a superposition of two hexagonal phases to a purely hexagonal phase at high concentrations. A relaxation, which is visible when no ibuprofen is present in the membrane, vanishes upon addition of ibuprofen. This we attribute to a stiffening of the membrane. This behavior may be instrumental in explaining the toxic behavior of ibuprofen in long-term application.

The effect of operational stressors on ibuprofen pharmacokinetics.

PubMed

Boscarino, Cathy; Edginton, Andrea N; Peng, Henry; Riggs, K Wayne; Szeitz, András; Cheung, Bob

2013-01-01

To determine whether two of the major operational stressors associated with military missions in Afghanistan: dry heat and long durations of soldier patrol (SP), alter the pharmacokinetics of ibuprofen. Thirteen healthy and physically fit participants (19-32 years) were randomized to a four-arm crossover study, as follows: Arm 4 consisted of a simulated 2.5 h SP on a treadmill set at 4.5 km/h, 2% incline (15-min walk/5-min rest cycle) in a climatic chamber set to 42°C, 9% relative humidity. Arm 3 was similar to arm 4 but at room temperature, and arms 1 and 2 were sham SP to 3 and 4, respectively. For the final 2.5 h, participants remained in a semi-supine position. Each participant orally administered one 400-mg Advil Liqui-Gel® capsule. Blood samples were drawn over time and analyzed for (R)-ibuprofen and (S)-plasma ibuprofen concentrations using UPLC/MS/MS. Concentration-time data were analyzed by compartmental methods. Exercise significantly decreased the t(1/2abs) (h) of (S)-ibuprofen (0.26 to 0.17; p = 0.015) and T(max) (h) for both (R)-ibuprofen (0.97 to 0.73; p = 0.008) and (S)-ibuprofen (1.13 to 0.84; p = 0.005). Values for t(lag) (h) also decreased with exercise for both (R)-ibuprofen (0.38 to 0.22; p = 0.005), and (S)-ibuprofen (0.39 to 0.23; p = 0.001). Exercise stress had a significant impact on the absorption profile of (R)- and (S)-ibuprofen. Excessive self-administration rate and dose may not be due to the military operational stressors of heat and soldier presence patrol.

Niosomes encapsulating Ibuprofen-cyclodextrin complexes: preparation and characterization.

PubMed

Marianecci, Carlotta; Rinaldi, Federica; Esposito, Sara; Di Marzio, Luisa; Carafa, Maria

2013-08-01

A new delivery system based on ibuprofen-β-cyclodextrin (βCd) complexation and its loading into non-ionic surfactant vesicles (NSVs) was developed to improve ibuprofen therapeutic efficacy in topical formulations. The proposed strategy exploits the well known solubilizing and stabilizing properties of cyclodextrins together with the high tolerability and percutaneous absorption enhancing properties of NSVs. The complexing capacity of Cds in the presence of Ibuprofen in aqueous solution was evaluated by means of phase solubility studies. The technique used to obtain solid ibuprofen-βCd complexes was the co-lyophilization method. The influence of the preparation method on the physicochemical properties of the final product was evaluated by means of Fourier Transform Infrared Spectroscopy and Differential scanning calorimetry studies. Ibuprofen-βCd complexes were included in Tween 20/Cholesterol vesicles and characterized in terms of size, zeta (ζ)-potential, stability, drug entrapment efficiency and drug release. The best ibuprofen-βCd-NSV system exhibited in vitro drug permeation properties significantly improved with respect to those of the plain drug suspension.

Sustained intra-articular release of celecoxib in an equine repeated LPS synovitis model.

PubMed

Cokelaere, Stefan M; Plomp, Saskia G M; de Boef, Esther; de Leeuw, Mike; Bool, Sophie; van de Lest, Chris H A; René van Weeren, P; Korthagen, Nicoline M

2018-05-02

Synovial inflammation is an important characteristic of arthritic disorders like osteoarthritis and rheumatoid arthritis. Orally administered non-steroidal anti-inflammatory drugs (NSAIDs) such as celecoxib are among the most widely prescribed drugs to manage these debilitating diseases. Intra-articular delivery in biodegradable in situ forming hydrogels overcomes adverse systemic effects and prolongs drug retention in the joint. In this study two formulations of celecoxib (40 mg/g and 120 mg/g) in a propyl-capped PCLA-PEG-PCLA triblock copolymer were sequentially evaluated in a multiple LPS challenge equine synovitis model. Intra-articular release and systemic exposure to celecoxib and local changes at joint level were evaluated longitudinally. A single intra-articular injection of the high dose (HCLB)-gel or low dose (LCLB)-gel showed a sustained and controlled intra-articular release in both inflamed and healthy joints together with very low systemic exposure. Synovitis and lameness were moderate respectively very mild in this model due to the low concentration LPS (0.25 ng/joint). Both celecoxib formulations had a mild, transient effect on inflammatory and structural synovial fluid biomarkers but these returned to baseline within one week of administration. The HCLB-gel showed a significant inhibition in peak white blood cell concentration at 8 hours after LPS induction. Elevated levels of celecoxib were observed in the joint for up to 30 days but no overall anti-inflammatory effects could be observed, which was thought to be due to the moderate synovitis. As there were no long-term adverse effects, sustained intra-articular release of celecoxib from in situ forming hydrogels should be evaluated further for its effects on longer-term relief of inflammatory joint pain in humans and animals. Copyright © 2018. Published by Elsevier B.V.

Interaction of celecoxib with different anti-cancer drugs is antagonistic in breast but not in other cancer cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

El-Awady, Raafat A., E-mail: relawady@sharjah.ac.ae; Department of Pharmacology and Pharmaceutics, College of Pharmacy, University of Sharjah, University City road, 27272 Sharjah; Saleh, Ekram M.

Celecoxib, an inhibitor of cyclooxygenase-2, is being investigated for enhancement of chemotherapy efficacy in cancer clinical trials. This study investigates the ability of cyclooxygenase-2 inhibitors to sensitize cells from different origins to several chemotherapeutic agents. The effect of the drug's mechanism of action and sequence of administration are also investigated. The sensitivity, cell cycle, apoptosis and DNA damage of five different cancer cell lines (HeLa, HCT116, HepG2, MCF7 and U251) to 5-FU, cisplatin, doxorubicin and etoposide {+-} celecoxib following different incubation schedules were analyzed. We found antagonism between celecoxib and the four drugs in the breast cancer cells MCF7 followingmore » all incubation schedules and between celecoxib and doxorubicin in all cell lines except for two combinations in HCT116 cells. Celecoxib with the other three drugs in the remaining four cell lines resulted in variable interactions. Mechanistic investigations revealed that celecoxib exerts different molecular effects in different cells. In some lines, it abrogates the drug-induced G2/M arrest enhancing pre-mature entry into mitosis with damaged DNA thus increasing apoptosis and resulting in synergism. In other cells, it enhances drug-induced G2/M arrest allowing time to repair drug-induced DNA damage before entry into mitosis and decreasing cell death resulting in antagonism. In some synergistic combinations, celecoxib-induced abrogation of G2/M arrest was not associated with apoptosis but permanent arrest in G1 phase. These results, if confirmed in-vivo, indicate that celecoxib is not a suitable chemosensitizer for breast cancer or with doxorubicin for other cancers. Moreover, combination of celecoxib with other drugs should be tailored to the tumor type, drug and administration schedule. - Graphical abstract: Display Omitted Highlights: > Celecoxib may enhance effects of anticancer drugs. > Its combination with four drugs was tested in five cancer

Detection and Analysis of the Quality of Ibuprofen Granules

NASA Astrophysics Data System (ADS)

Yu-bin, Ji; Xin, LI; Guo-song, Xin; Qin-bing, Xue

2017-12-01

The Ibuprofen Granules comprehensive quality testing to ensure that it is in accordance with the provisions of Chinese pharmacopoeia. With reference of Chinese pharmacopoeia, the Ibuprofen Granules is tested by UV, HPLC, in terms of grain size checking, volume deviation, weight loss on drying detection, dissolution rate detection, and quality evaluation. Results indicated that Ibuprofen Granules conform to the standards. The Ibuprofen Granules are qualified and should be permitted to be marketed.

Ursodeoxycholic acid counteracts celecoxib in reduction of duodenal polyps in patients with familial adenomatous polyposis: a multicentre, randomized controlled trial

PubMed Central

2013-01-01

Background Due to prophylactic colectomy, mortality in patients with familial adenomatous polyposis (FAP) has changed, with duodenal cancer currently being the main cause of death. Although celecoxib reduces duodenal polyp density in patients with FAP, its long-term use may increase the risk of cardiovascular events and alternatives need to be explored. Preclinical studies suggest that the combination of celecoxib with ursodeoxycholic acid (UDCA) is a potentially effective strategy. We performed a randomized, double-blind, placebo-controlled trial to investigate the effect of celecoxib and UDCA co-treatment on duodenal adenomatosis in patients with FAP. Methods Patients with FAP received celecoxib (400 mg twice daily) and UDCA (1000-2000 mg daily, ~20-30 mg/kg/day, n=19) or celecoxib and placebo (n=18) orally for 6 months. Primary outcome was drug efficacy, assessed by comparing duodenal polyp density at pre- and post-intervention by blinded review of endoscopic recordings. As secondary outcomes, cell proliferation, apoptosis, and COX-2 levels in normal duodenal mucosa were assessed by immunohistochemistry or real-time quantitative polymerase chain reaction. Results In intention-to-treat analysis, deceased polyp density was observed after celecoxib/placebo treatment (p=0.029), whereas increased polyp density was observed after celecoxib/UDCA treatment (p=0.014). The difference in change in duodenal polyp density was statistically significant between the groups (p=0.011). No changes in secondary outcomes were observed. Thirty patients (81%) reported one or more adverse events, 16 patients (84%, Common Toxicity Criteria for Adverse Events version 3.0 (CTCAE) grade 1–3) treated with celecoxib/UDCA and 14 patients (78%, CTCAE grade 1–2) treated with celecoxib/placebo. Nine patients (24%) discontinued intervention prematurely, 5 patients (26%) treated with celecoxib/UDCA and 4 patients (22%) treated with celecoxib/placebo. Conclusions Celecoxib reduces duodenal

Cell Cycle Target-based Therapy for Ovarian Cancer

DTIC Science & Technology

2008-09-01

induces apoptosis in quiescent ovarian cancer cells. Strong inducers of apoptosis included flufenamic acid, flurbiprofen, celebrex and finasteride ...Thus, a whole panel of NSAIDs including Aspirin, Ibuprofen, Exisulind, Acetaminophen, Naproxen, NS-398, Celecoxib, Diclofenac, Finasteride ...Naproxen, 200µM NS-398, 50µM Celecoxib, 200µM Diclofenac, 50µM Finasteride , 200µM Flufenamic acid, 40µM Meloxican, 50µM Ebselen, 20nM Flurbiprofen or

Inhibition of bacterial multidrug resistance by celecoxib, a cyclooxygenase-2 inhibitor.

PubMed

Kalle, Arunasree M; Rizvi, Arshad

2011-01-01

Multidrug resistance (MDR) is a major problem in the treatment of infectious diseases and cancer. Accumulating evidence suggests that the cyclooxygenase-2 (COX-2)-specific inhibitor celecoxib would not only inhibit COX-2 but also help in the reversal of drug resistance in cancers by inhibiting the MDR1 efflux pump. Here, we demonstrate that celecoxib increases the sensitivity of bacteria to the antibiotics ampicillin, kanamycin, chloramphenicol, and ciprofloxacin by accumulating the drugs inside the cell, thus reversing MDR in bacteria.

An Overview of Clinical Pharmacology of Ibuprofen

PubMed Central

Bushra, Rabia; Aslam, Nousheen

2010-01-01

Ibuprofen was the first member of Propionic acid derivatives introduced in 1969. It is a popular domestic and over the counter analgesic and antipyretic for adults and children. Ibuprofen has been rated as the safest conventional NSAID by spontaneous adverse drug reaction reporting systems in the UK. This article summarizes the main pharmacological effects, therapeutical applications and adverse drug reactions, drug-drug interactions and food drug interactions of ibuprofen that have been reported especially during the last 10 years. PMID:22043330

Ibuprofen: from invention to an OTC therapeutic mainstay.

PubMed

Rainsford, K D

2013-01-01

The discovery of ibuprofen's anti-inflammatory activity by Dr (now Professor) Stewart Adams and colleagues (Boots Pure Chemical Company Ltd, Nottingham, UK) 50 years ago represented a milestone in the development of anti-inflammatory analgesics. Subsequent clinical studies were the basis for ibuprofen being widely accepted for treating painful conditions at high anti-rheumatic doses (≤ 2400 mg/d), with lower doses (≤ 1200 mg/d for ≤ 10 days) for mild-moderate acute pain (e.g. dental pain, headache, dysmenorrhoea, respiratory symptoms and acute injury). The early observations have since been verified in studies comparing ibuprofen with newer cyclo-oxygenase-2 selective inhibitors ('coxibs'), paracetamol and other non-steroidal anti-inflammatory drugs (NSAIDs). The use of the low-dose, non-prescription, over-the-counter (OTC) drug was based on marketing approval in 1983 (UK) and 1984 (USA); and it is now available in over 80 countries. The relative safety of OTC ibuprofen has been supported by large-scale controlled studies. It has the same low gastro-intestinal (GI) effects as paracetamol (acetaminophen) and fewer GI effects than aspirin. Ibuprofen is a racemate. Its physicochemical properties and the short plasma-elimination half-life of the R(-) isomer, together with its limited ability to inhibit cyclo-oxygenase-1 (COX-1) and thus prostaglandin (PG) synthesis, compared with that of S(+)-ibuprofen, are responsible for the relatively low GI toxicity. The R(-) isomer is then converted in the body to the S(+) isomer after absorption in the GI tract. Ex vivo inhibition of COX-1 (thromboxane A(2)) and COX-2 (PGE(2)) at the plasma concentrations of S(+)-ibuprofen corresponding to those found in the plasma following ingestion of 400 mg ibuprofen in dental and other inflammatory pain models provides evidence of the anti-inflammatory mechanism at OTC dosages. R(-)-ibuprofen has effects on leucocytes, suggesting that ibuprofen has anti-leucocyte effects, which

Encapsulation of Ibuprofen in CD-MOF and Related Bioavailability Studies.

PubMed

Hartlieb, Karel J; Ferris, Daniel P; Holcroft, James M; Kandela, Irawati; Stern, Charlotte L; Nassar, Majed S; Botros, Youssry Y; Stoddart, J Fraser

2017-05-01

Although ibuprofen is one of the most widely used nonsteroidal anti-inflammatory drugs (NSAIDs), it exhibits poor solubility in aqueous and physiological environments as a free acid. In order to improve its oral bioavailability and rate of uptake, extensive research into the development of new formulations of ibuprofen has been undertaken, including the use of excipients as well as ibuprofen salts, such as ibuprofen lysinate and ibuprofen, sodium salt. The ultimate goals of these studies are to reduce the time required for maximum uptake of ibuprofen, as this period of time is directly proportional to the rate of onset of analgesic/anti-inflammatory effects, and to increase the half-life of the drug within the body; that is, the duration of action of the effects of the drug. Herein, we present a pharmaceutical cocrystal of ibuprofen and the biocompatible metal-organic framework called CD-MOF. This metal-organic framework (MOF) is based upon γ-cyclodextrin (γ-CD) tori that are coordinated to alkali metal cations (e.g., K + ions) on both their primary and secondary faces in an alternating manner to form a porous framework built up from (γ-CD) 6 cubes. We show that ibuprofen can be incorporated within CD-MOF-1 either by (i) a crystallization process using the potassium salt of ibuprofen as the alkali cation source for production of the MOF or by (ii) absorption and deprotonation of the free-acid, leading to an uptake of 23-26 wt % of ibuprofen within the CD-MOF. In vitro viability studies revealed that the CD-MOF is inherently not affecting the viability of the cells with no IC 50 value determined up to a concentration of 100 μM. Bioavailability investigations were conducted on mice, and the ibuprofen/CD-MOF pharmaceutical cocrystal was compared to control samples of the potassium salt of ibuprofen in the presence and absence of γ-CD. From these animal studies, we observed that the ibuprofen/CD-MOF-1 cocrystal exhibits the same rapid uptake of ibuprofen as the

Cell Cycle Target-Based Therapy of Ovarian Cancer

DTIC Science & Technology

2008-03-01

inducers of apoptosis included flufenamic acid, flurbiprofen, celebrex and finasteride , whereas treatment with ibuprofen in low levels of apoptosis...Ibuprofen, Exisulind, Acetaminophen, Naproxen, NS-398, Celecoxib, Diclofenac, Finasteride , Flufenamic acid, Meloxican, Ebselen and Flurbiprofen was...Diclofenac, 50µM Finasteride , 200µM Flufenamic acid, 40µM Meloxican, 50µM Ebselen, 20nM Flurbiprofen or 50µM Sulindac sulfide. Apoptosis was measured 24

Enhanced rectal bioavailability of ibuprofen in rats by poloxamer 188 and menthol.

PubMed

Yong, Chul Soon; Yang, Chae Ha; Rhee, Jong-Dal; Lee, Beom-Jin; Kim, Dong-Chool; Kim, Dae-Duk; Kim, Chong-Kook; Choi, Jun-Shik; Choi, Han-Gon

2004-01-09

To improve the bioavailability of poorly water-soluble ibuprofen in the rectum with poloxamer and menthol, the effects of menthol and poloxamer 188 on the aqueous solubility of ibuprofen were investigated. The dissolution and pharmacokinetic study of ibuprofen delivered by the poloxamer gels composed of poloxamer 188 and menthol were then performed. In the absence of poloxamer, the solubility of ibuprofen increased until the ratio of menthol to ibuprofen increased from 0:10 to 4:6 followed by an abrupt decrease in solubility above the ratio of 4:6, indicating that four parts menthol formed eutectic mixture with six parts ibuprofen. In the presence of poloxamer, the solutions with the same ratio of menthol to ibuprofen showed abrupt increase in the solubility of ibuprofen. The poloxamer gel with menthol/ibuprofen ratio of 1:9 and higher than 15% poloxamer 188 showed the maximum solubility of ibuprofen, 1.2mg/ml. Menthol improved the dissolution rates of ibuprofen from poloxamer gels. Release mechanism showed that the release rate of ibuprofen from the poloxamer gels without menthol was independent of the time but the drug might be released from the poloxamer gels with menthol by Fickian diffusion. Furthermore, the poloxamer gel with menthol (poloxamer/menthol/ibuprofen (15%/0.25%/2.5%)) gave significantly higher initial plasma concentrations, C(max) and AUC of ibuprofen than did solid suppository, indicating that the drug from poloxamer gel could be more absorbed than that from solid one in rats. Thus, the poloxamer gel with poloxamer 188 and menthol was a more effective rectal dosage form for ibuprofen.

Modeling the onset and offset of dental pain relief by ibuprofen.

PubMed

Li, Hanbin; Mandema, Jaap; Wada, Russell; Jayawardena, Shyamalie; Desjardins, Paul; Doyle, Geraldine; Kellstein, David

2012-01-01

Onset and offset of dental pain relief by ibuprofen following third molar extraction were modeled in a randomized, double-blind, placebo-controlled, parallel-group, 8-hour study of patients receiving either a novel effervescent ibuprofen tablet (400 mg; N = 30), standard ibuprofen tablets (Nurofen(®) 2 × 200 mg; N = 22), or placebo (N = 37). An Emax model was fit to pain relief scores. Linear hazard models were used to analyze the time to first perceptible relief (TFPR), the time to meaningful pain relief (TMPR), and time to remedication (REMD). Nomograms were created to correlate TFPR, TMPR, and REMD with different ibuprofen pharmacokinetic profiles. Effervescent ibuprofen was absorbed rapidly with 95% completion within 15 minutes. Maximum pain relief score by ibuprofen was 1.8 units greater than placebo, with an EC50 (effect-site) for ibuprofen concentration of 10.2 µg·mL(-1). The likelihood to achieve TFPR and TMPR was doubled for every 10 µg·mL(-1) increase in ibuprofen plasma concentration. REMD risk decreased 40-fold as the categorical pain relief score increased from 0 to 3. Rapid absorption of ibuprofen effervescent resulted in an earlier TFPR and TMPR, and a lower REMD rate than standard ibuprofen. The nomograms may be useful in predicting the onset and offset of new faster acting ibuprofen formulations, based on pharmacokinetic profiles.

Celecoxib induces proliferation and Amphiregulin production in colon subepithelial myofibroblasts, activating erk1-2 signaling in synergy with EGFR.

PubMed

Benelli, Roberto; Venè, Roberta; Minghelli, Simona; Carlone, Sebastiano; Gatteschi, Beatrice; Ferrari, Nicoletta

2013-01-01

The COX-2 inhibitor Celecoxib, tested in phase III trials for the prevention of sporadic colon adenomas, reduced the appearance of new adenomas, but was unable to affect the incidence of colon cancer. Moreover the 5years follow-up showed that patients discontinuing Celecoxib treatment had an increased incidence of adenomas as compared to the placebo arm. In the APC(min/+) mouse model short term treatment with Celecoxib reduced gut adenomas, but a prolonged administration of the drug induced fibroblast activation and intestinal fibrosis with a final tumor burden. The way Celecoxib could directly activate human colon myofibroblasts (MF) has not yet been investigated. We found that MF are activated by non toxic doses of Celecoxib. Celecoxib induces erk1-2 and Akt phosphorylation within 5'. This short term activation is apparently insufficient to cause phenotypic changes, but the contemporary triggering of EGFR causes an impressive synergic effect inducing MF proliferation and the neo-expression and release of Amphiregulin (AREG), a well known EGFR agonist involved in colon cancer progression. As a confirm to these observations, the erk inhibitor U0126 and the EGFR inhibitors Tyrphostin and Cetuximab were able to contrast AREG induction. Our data provide evidence that Celecoxib directly activates MF empowering EGFR signaling. According to these results the association with EGFR (or erk1-2) inhibitors could abolish the off-target activity of Celecoxib, possibly extending the potential of this drug for colon cancer prevention. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Efficacy of Celecoxib for Early Postoperative Pain Management in Hip Arthroscopy: A Prospective Randomized Placebo-Controlled Study.

PubMed

Kahlenberg, Cynthia A; Patel, Ronak M; Knesek, Michael; Tjong, Vehniah K; Sonn, Kevin; Terry, Michael A

2017-06-01

To determine whether 400 mg of celecoxib administered 1 hour before hip arthroscopy surgery would reduce pain, provide reduction in overall narcotic consumption, and lead to more rapid discharge from recovery rooms. Ninety-eight patients were randomized to either the celecoxib group (n = 50) or the placebo group (n = 48). An a priori power analysis was done set to detect a difference of 0.50 on the visual analog scale (VAS), based on the senior author's preference. The number of patients planned for recruitment was rounded up to 100 to allow for flexibility in the study. Inclusion criteria were any patient at least 18 years old who underwent hip arthroscopy surgery performed by the senior author. All patients had less than Tönnis grade 2 arthritis. Exclusion criteria were allergy to sulfa-based drugs, prior adverse reaction to celecoxib, or patients who were on chronic narcotics for whom alternative pain management regimens were arranged before surgery. Randomization was performed on a 1:1 basis in blocks of 10 using sealed envelopes stating celecoxib or placebo. One hour before surgery, all patients received either 400 mg celecoxib or placebo. Patients were evaluated using a VAS preoperatively, immediately postoperatively, and at 1 and 2 hours postoperatively. Time from the operating room to "ready for discharge" and number of morphine equivalents of narcotic medication required in the postanesthesia care unit were recorded. Age and preoperative VAS were similar between the celecoxib and placebo control group, with average ages of 34.2 ± 11.9 and 35.8 ± 11.6 (P = .27) and preoperative VAS of 2.1 ± 2.06 and 2.3 ± 1.98 (P = .29), respectively. The celecoxib group had 26 females and 24 males, whereas the placebo group had 29 females and 19 males (P = .42). The most common surgical procedures were labral repair (31 patients in the celecoxib group and 29 patients in the placebo group), and labral repair with acetabular osteoplasty (13 patients in the

Single dose oral ibuprofen plus paracetamol (acetaminophen) for acute postoperative pain.

PubMed

Derry, Christopher J; Derry, Sheena; Moore, R Andrew

2013-06-24

Combining two different analgesics in fixed doses in a single tablet can provide better pain relief than either drug alone in acute pain. This appears to be broadly true across a range of different drug combinations, in postoperative pain and migraine headache. Some combinations of ibuprofen and paracetamol are available for use without prescription in some acute pain situations. To assess the efficacy and adverse effects of single dose oral ibuprofen plus paracetamol for acute postoperative pain using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (Issue 4 of 12, 2013), MEDLINE (1950 to May 21st 2013), EMBASE (1974 to May 21st 2013), the Oxford Pain Database, ClinicalTrials.gov, and reference lists of articles. Randomised, double-blind clinical trials of single dose, oral ibuprofen plus paracetamol compared with placebo or the same dose of ibuprofen alone for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed quality, and extracted data. We used validated equations to calculate the area under the pain relief versus time curve and derive the proportion of participants with at least 50% of maximum pain relief over six hours. We calculated relative risk (RR) and number needed to treat to benefit (NNT) for ibuprofen plus paracetamol, ibuprofen alone, or placebo. We used information on use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse events. Searches identified three studies involving 1647 participants. Each of them examined several dose combinations. Included studies provided data from 508 participants for the comparison of ibuprofen 200 mg + paracetamol 500 mg with placebo, 543

Ibuprofen results in alterations of human fetal testis development

PubMed Central

Ben Maamar, Millissia; Lesné, Laurianne; Hennig, Kristin; Desdoits-Lethimonier, Christèle; Kilcoyne, Karen R.; Coiffec, Isabelle; Rolland, Antoine D.; Chevrier, Cécile; Kristensen, David M.; Lavoué, Vincent; Antignac, Jean-Philippe; Le Bizec, Bruno; Dejucq-Rainsford, Nathalie; Mitchell, Rod T.; Mazaud-Guittot, Séverine; Jégou, Bernard

2017-01-01

Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7–17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8–9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10–12 GW, or in second trimester xenografted testes (14–17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow ‘early window’ of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology. PMID:28281692

Tumor-associated down-regulation of 15-lipoxygenase-1 is reversed by celecoxib in colorectal cancer.

PubMed

Heslin, Martin J; Hawkins, Ashley; Boedefeld, William; Arnoletti, J Pablo; Frolov, Andrey; Soong, Richie; Urist, Marshall M; Bland, Kirby I

2005-06-01

To evaluate the role of celecoxib on 15-lipoxygenase-1 (15-LOX-1) expression, protein levels, and rates of apoptosis in colorectal cancer cell lines. Also, to evaluate the expression of 15-LOX-1 in human normal mucosa, adenoma, and carcinoma with correlation to overall survival. The function of 15-LOX-1 is to maintain normal rates of apoptosis (programmed cell death). Decreased apoptosis is one mechanism of cancer growth and dissemination. It is our hypothesis that expression of 15-LOX-1 is reduced in human colorectal cancer (CRC) and the administration of celecoxib can reverse this process and induce apoptosis. Effect of celecoxib in cell culture: The effect of 40 micromol/L celecoxib was compared with untreated controls in tissue culture utilizing HT-29 and DLD-1 CRC cell lines. Expression of 15-LOX-1 protein was measured by immunoblot. Induction of apoptosis was evaluated by annexin V staining. All data are presented as mean +/- SEM, with significance defined as P < 0.05. 15-LOX-1 in human CRC: From February 1998 to January 2002, 126 patients underwent surgical resection of either colorectal adenomas (n = 24) or carcinomas (n = 102), or both (n = 25). Tissue was macrodissected, snap frozen, and stored at -80 degrees C. After tissue processing, RNA was extracted and gene expression of 15-LOX-1 was quantified utilizing ABI prism real-time quantitative RT-PCR. Significance evaluated by the Wilcoxon signed rank test. Effect of celecoxib in cell culture: After 72 hours of treatment with celecoxib, immunoblot demonstrated a 1.5- to 2-fold increase in 15-LOX-1 protein expression in HT-29 and DLD-1 cells, respectively. Celecoxib produced greater than a 2-fold increase in the rate of apoptosis compared with control cells in both cell lines (P < 0.05). 15-LOX-1 in human CRC: The mean age of the patients was 62 +/- 1 years; 78% were white and 48% were female. The mean size of the polyps and cancers were 3.0 +/- 0.4 and 5.0 +/- 0.1 cm, respectively. Expression of 15-LOX-1

Ibuprofen timing for hand surgery in ambulatory care

PubMed Central

Giuliani, Enrico; Bianchi, Anna; Marcuzzi, Augusto; Landi, Antonio; Barbieri, Alberto

2015-01-01

OBJECTIVE: To evaluate the effect of pre-operative administration of ibuprofen on post-operative pain control vs. early post-operative administration for hand surgery procedures performed under local anaesthesia in ambulatory care. METHODS: Candidates to trigger finger release by De Quervain tenosynovitis and carpal tunnel operation under local anesthesia were enrolled in the study. Group A received 400 mg ibuprofen before the operation and placebo after the procedure; group B received placebo before the operation and ibuprofen 400 mg at the end of the procedure; both groups received ibuprofen 400 mg every 6h thereafter. Visual analogue scale (VAS) was measured at fixed times before and every 6h after surgery, for a total follow-up of 18h. RESULTS: Groups were similar according to age, gender and type of surgery. Median VAS values did not produce any statistical significance, while there was a statistically significant difference on pre-operative and early post-operative VAS values between groups (A -8.53 mm vs. B 3.36 mm, p=0.0085). CONCLUSION: Average pain levels were well controlled by local anesthesia and post-operative ibuprofen analgesia. Pre-operative ibuprofen administration can contribute to improve early pain management. Level of Evidence II, Therapeutic Studies. PMID:26327799

Celecoxib Monotherapy Maintained Small Intestinal Mucosa Better Compared With Loxoprofen Plus Lansoprazole Treatment: A Double-blind, Randomized, Controlled Trial.

PubMed

Fujimori, Shunji; Hanada, Ryuzo; Hayashida, Mari; Sakurai, Toshiyuki; Ikushima, Ippei; Sakamoto, Choitsu

2016-03-01

The aim of this study was to compare celecoxib with loxoprofen for protection of small intestine. RCT studies report that COX-2 selective inhibitor celecoxib induces fewer small intestinal injuries than nonselective nonsteroidal anti-inflammatory drugs (NSAIDs). Loxoprofen is a prodrug nonselective NSAID developed to protect upper gastrointestinal tract. A total of 150 healthy volunteers (40 to 70 y) were enrolled. After medical checkup including laboratory data, subjects were randomly assigned to celecoxib (200 mg daily) or loxoprofen (180 mg daily) plus lansoprazole (15 mg daily). All drugs were prepared using inactive capsules. After randomization, all subjects were first examined by baseline capsule endoscopy (CE). After 14 days, subjects underwent posttreatment CE. We compared baseline and posttreatment CE findings of the 2 groups. All CE data were evaluated blindly by 3 reviewers. Pretreatment and posttreatment laboratory variables were also compared. A total of 74 subjects (49±6 y, F/M: 36/38) were enrolled in celecoxib group and 76 subjects (49±7 y, F/M: 39/37)in loxoprofen group. Five in celecoxib group and 4 in loxoprofen group were excluded from CE analysis mainly due to incomplete CE. The percentage of subjects with at least 1 posttreatment mucosal break was lower in celecoxib group (10%) than in loxoprofen group (49%) (P<0.0001). A total of 0.3±1.0 posttreatment small intestinal mucosal breaks were detected in the celecoxib group, and 6.8±21.5 in the loxoprofen group (P<0.0001). Posttreatment hemoglobin concentration in loxoprofen group (5.1% reduction) was lower compared with celecoxib group (2.1% reduction) (P=0.006). In terms of protection of small intestine from NSAIDs toxicity, celecoxib monotherapy was superior to loxoprofen+lansoprazole combination therapy (UMIN: 000007936).

The economic and clinical burden of early versus late initiation of celecoxib among patients with osteoarthritis

PubMed Central

Shelbaya, Ahmed; Solem, Caitlyn T; Walker, Chris; Wan, Yin; Johnson, Courtney; Cappelleri, Joseph C

2018-01-01

Objective This study aimed to evaluate the characteristics associated with early versus late initiation of celecoxib treatment after osteoarthritis (OA) diagnosis and whether economic and safety outcomes differ between patients with early versus late initiation of celecoxib. Methods Adults (≥18 years) with a confirmed OA diagnosis (International Classification of Diseases, 9th Edition, Clinical Modifications code: 715.XX), ≥12 months of continuous pre- and post-index enrollment, and ≥1 post-index claim for celecoxib were included from the MarketScan® Commercial Claims and Encounter Database (2009–2013). Index date was defined as initial OA diagnosis. Patients were categorized as initiating celecoxib early (within 6 months of index date) or late (≥6 months after index date). Logistic regressions were used to assess characteristics associated with early versus late celecoxib initiation. Key outcomes included health care resource utilization (HCRU) and costs post-index, and adverse event incidence post-celecoxib initiation. Unadjusted and adjusted comparisons (using generalized linear models with a gamma distribution for costs and Poisson distribution for event and resource utilization) were made between early and late celecoxib initiators. Results Of the 62,434 OA patients identified, 27,402 were early and 35,032 were late initiators. Post-index hospital admissions and length of stay did not differ statistically between early versus late initiators after controlling for pre-index event rates and covariates, but early patients had significantly fewer outpatient (incidence rate ratio [IRR]: 0.96; 95% confidence interval [CI]: 0.95, 0.97) and emergency room visits (IRR: 0.89; 95% CI: 0.84, 0.95). After adjustment for key covariates, early initiators (versus late initiators) had lower all-cause (US$12,909 versus US$13,781, P<0.001) and OA-related (US$4,988 versus US$5,178, P=0.015) costs per person-year. Early initiators had no statistically significant

A parallel-group comparison study of celecoxib with loxoprofen sodium in third mandibular molar extraction patients.

PubMed

Yamashita, Y; Sano, N; Shimohira, D; Danjo, A; Goto, M

2014-12-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are used widely, but they may damage the upper gastrointestinal mucosa owing to their mechanism of action. Selective cyclooxygenase 2 (COX-2) inhibitors are known to have a reduced risk for such damage. In this comparative study, the efficacy and safety of the selective COX-2 inhibitor celecoxib for pain after third mandibular molar extraction were compared with those of loxoprofen sodium. This was a parallel-group comparison study; 107 patients who had undergone third mandibular molar extraction were given celecoxib and 102 were given loxoprofen. The level of pain on a visual analogue scale (VAS) 15 min and 30 min after taking the experimental drug decreased over time, with no significant difference between the two groups. The percentage of patients taking a second dose was 64.5% for celecoxib and 80.4% for loxoprofen. The time to second dose was significantly longer for celecoxib (533.5 min) than for loxoprofen (387.4 min). There was no significant difference in the patients' impression of efficacy between the two groups, with ratings of 'excellent' and 'good' for 77.4% in the loxoprofen group and 74.5% in the celecoxib group. These results demonstrate that celecoxib is of equal clinical value to loxoprofen for acute pain after third mandibular molar extraction. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Efficacy of Ibuprofen and ibuprofen/acetaminophen on postoperative pain in symptomatic patients with a pulpal diagnosis of necrosis.

PubMed

Wells, L Kevin; Drum, Melissa; Nusstein, John; Reader, Al; Beck, Mike

2011-12-01

The purpose of this prospective, randomized, double-blind study was to determine ibuprofen versus ibuprofen/acetaminophen use for postoperative endodontic pain in symptomatic patients with a pulpal diagnosis of necrosis and an associated periapical radiolucency who were experiencing moderate to severe preoperative pain. We also recorded escape medication use. Seventy-one adult patients presenting for emergency endodontic treatment with a symptomatic maxillary or mandibular tooth with a pulpal diagnosis of necrosis, periapical radiolucent area, and moderate to severe pain participated in this study. The patients were randomly divided into 2 groups by random assignment and numeric coding. An emergency debridement of the tooth was completed with hand and rotary instrumentation. At the end of the appointment, the patients randomly received capsules of either 600 mg ibuprofen or 600 mg ibuprofen combined with 1000 mg acetaminophen (blinded to both operator and patient). Patients also received a 6-day diary to be completed after anesthesia wore off and every morning for 5 days. Patients were asked to record pain, symptoms, and the number of capsules taken. Patients received escape medication (Vicodin) if the study medication did not control their pain. Postoperative data were analyzed by randomization test and step-down Bonferroni method of Holm. There were decreases in pain levels and analgesic use over time for the ibuprofen and ibuprofen/acetaminophen groups. There was no statistically significant difference between the 2 groups for analgesic use or escape medication use. Approximately 20% of patients in both groups required escape medication to control pain. Copyright © 2011 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Spectrofluorimetric study of the beta-cyclodextrin-ibuprofen complex and determination of ibuprofen in pharmaceutical preparations and serum.

PubMed

Hergert, L A; Escandar, G M

2003-06-13

The inclusion complexation of ibuprofen in beta-cyclodextrin (beta-CD) has been examined by means of spectrofluorimetry at both acid and alkaline pH. The results suggest that stable 1:1 complexes are formed in both media. The analysis of the pK(a) values for ibuprofen in both the absence and presence of beta-CD (4.12 and 4.66, respectively) suggests that in the inclusion complex the carboxylic group is located outside the cyclodextrin (CD) but interacting with it. Further structural characterization of the complex was carried out by means of am1 semiempiral calculations. Based on the obtained results, a spectrofluorimetric method for the determination of ibuprofen in the presence of beta-CD at 10 degrees C was developed in the range of 4.7-58 mug ml(-1). Better limits of detection (1.6 mug ml(-1)) and quantification (4.7 mug ml(-1)) were obtained in this latter case with respect to those obtained in the absence of beta-CD. The method was satisfactorily applied to the quantification of ibuprofen in pharmaceutical preparations. A novel spectrofluorimetric determination of ibuprofen in the presence of beta-CD was also developed for serum samples at concentration levels between 5 and 70 mug ml(-1). It uses second-order fluorescence excitation-emission matrices coupled to an algorithm based on self-weighted alternating trilinear decomposition (SWATLD), and avoids resorting to separative instrumental analyses.

CELECOXIB ATTENUATES SYSTEMIC LIPOPOLYSACCHARIDE-INDUCED BRAIN INFLAMMATION AND WHITE MATTER INJURY IN THE NEONATAL RATS

PubMed Central

FAN, L.-W.; KAIZAKI, A.; TIEN, L.-T.; PANG, Y.; TANAKA, S.; NUMAZAWA, S.; BHATT, A. J.; CAI, Z.

2013-01-01

Lipopolysaccharide (LPS)-induced white matter injury in the neonatal rat brain is associated with inflammatory processes. Cyclooxygenase-2 (COX-2) can be induced by inflammatory stimuli, such as cytokines and pro-inflammatory molecules, suggesting that COX-2 may be considered as the target for anti-inflammation. The objective of the present study was to examine whether celecoxib, a selective COX-2 inhibitor, can reduce systemic LPS-induced brain inflammation and brain damage. Intraperitoneal (i.p.) injection of LPS (2 mg/kg) was performed in postnatal day 5 (P5) of Sprague-Dawley rat pups and celecoxib (20 mg/kg) or vehicle was administered i.p. 5 min after LPS injection. The body weight and wire hanging maneuver test were performed 24 hr after the LPS exposure, and brain injury was examined after these tests. Systemic LPS exposure resulted in an impairment of behavioral performance and acute brain injury, as indicated by apoptotic death of oligodendrocytes (OLs) and loss of OL immunoreactivity in the neonatal rat brain. Treatments with celecoxib significantly reduced systemic LPS-induced neurobehavioral disturbance and brain damage. Celecoxib administration significantly attenuated systemic LPS-induced increments in the number of activated microglia and astrocytes, concentrations of IL-1β and TNFα, and protein levels of phosphorylated-p38 MAPK in the neonatal rat brain. The protection of celecoxib was also associated with a reduction of systemic LPS-induced COX-2+ cells which were double labeled with GFAP+ (astrocyte) cells. The overall results suggest that celecoxib was capable of attenuating the brain injury and neurobehavioral disturbance induced by systemic LPS exposure, and the protective effects are associated with its anti-inflammatory properties. PMID:23485816

Comparing Gabapentin and Celecoxib in Pain Management and Complications After Laminectomy: A Randomized Double-Blind Clinical Trial.

PubMed

Vasigh, Aminolah; Najafi, Fatemeh; Khajavikhan, Javaher; Jaafarpour, Molouk; Khani, Ali

2016-02-01

Complications and postoperative pain are major care problems that can affect the quality of health care plan. According to the use of multimodal therapy the current study aimed to compare the efficacy of gabapentin and celecoxib in pain management and complications after laminectomy at Ilam University of Medical Sciences, Ilam, Iran, in 2015. In this randomized double-blind clinical trial, 114 patients scheduled for elective laminectomy with simple random sampling design received gabapentin (n = 38, 900 mg/day), celecoxib (n = 38, 600 mg/day) and placebo (n = 38, capsule contain starch). Visual analog scale (VAS) was used to determine the intensity of pain. Complications after surgery, anxiety scores before surgery and patient's satisfaction 24 hours after the surgery were recorded. The mean pain intensity in the gabapentin group was lower compared to those of the placebo and celecoxib groups respectively at different time durations (P < 0.001). The means of morphine consumption were 11.9 mg, 22.8 mg and 30.1 mg in the gabapentin, celecoxib and placebo groups, respectively (P < 0.001). The prevalence of shivering, nausea, vomiting and pruritus were 10.5%, 12.8%, 10.3% and 18.4% in the gabapentin group vs 31.5%, 29.8%, 32.4% and 28.9% in the celecoxib group and 42.1%, 44.7%, 39.5% and 44.7% in the placebo group (P < 0.001). The mean anxiety score in the gabapentin group was 2.4 vs those of the celecoxib group 3 and placebo group 3.6 (P < 0.001). The frequencies of drowsiness were 42.1%, 13.2% and 5.3% in the gabapentin, celecoxib and placebo groups, respectively (P < 0.001). In the gabapentin group, patient satisfaction was significantly higher compared to those of the placebo and celecoxib groups (P < 0.05). According to the effect of gabapentin on pain management, complications after laminectomy and increased patients satisfaction, it can be regarded as an alter native in multimodal analgesia.

Comparing Gabapentin and Celecoxib in Pain Management and Complications After Laminectomy: A Randomized Double-Blind Clinical Trial

PubMed Central

Vasigh, Aminolah; Najafi, Fatemeh; Khajavikhan, Javaher; Jaafarpour, Molouk; Khani, Ali

2016-01-01

Background Complications and postoperative pain are major care problems that can affect the quality of health care plan. Objectives According to the use of multimodal therapy the current study aimed to compare the efficacy of gabapentin and celecoxib in pain management and complications after laminectomy at Ilam University of Medical Sciences, Ilam, Iran, in 2015. Patients and Methods In this randomized double-blind clinical trial, 114 patients scheduled for elective laminectomy with simple random sampling design received gabapentin (n = 38, 900 mg/day), celecoxib (n = 38, 600 mg/day) and placebo (n = 38, capsule contain starch). Visual analog scale (VAS) was used to determine the intensity of pain. Complications after surgery, anxiety scores before surgery and patient’s satisfaction 24 hours after the surgery were recorded. Results The mean pain intensity in the gabapentin group was lower compared to those of the placebo and celecoxib groups respectively at different time durations (P < 0.001). The means of morphine consumption were 11.9 mg, 22.8 mg and 30.1 mg in the gabapentin, celecoxib and placebo groups, respectively (P < 0.001). The prevalence of shivering, nausea, vomiting and pruritus were 10.5%, 12.8%, 10.3% and 18.4% in the gabapentin group vs 31.5%, 29.8%, 32.4% and 28.9% in the celecoxib group and 42.1%, 44.7%, 39.5% and 44.7% in the placebo group (P < 0.001). The mean anxiety score in the gabapentin group was 2.4 vs those of the celecoxib group 3 and placebo group 3.6 (P < 0.001). The frequencies of drowsiness were 42.1%, 13.2% and 5.3% in the gabapentin, celecoxib and placebo groups, respectively (P < 0.001). In the gabapentin group, patient satisfaction was significantly higher compared to those of the placebo and celecoxib groups (P < 0.05). Conclusions According to the effect of gabapentin on pain management, complications after laminectomy and increased patients satisfaction, it can be regarded as an alter native in multimodal analgesia. PMID

Celecoxib increases SMN and survival in a severe spinal muscular atrophy mouse model via p38 pathway activation.

PubMed

Farooq, Faraz; Abadía-Molina, Francisco; MacKenzie, Duncan; Hadwen, Jeremiah; Shamim, Fahad; O'Reilly, Sean; Holcik, Martin; MacKenzie, Alex

2013-09-01

The loss of functional Survival Motor Neuron (SMN) protein due to mutations or deletion in the SMN1 gene causes autosomal recessive neurodegenerative spinal muscle atrophy (SMA). A potential treatment strategy for SMA is to upregulate the amount of SMN protein originating from the highly homologous SMN2 gene, compensating in part for the absence of the functional SMN1 gene. We have previously shown that in vitro activation of the p38 pathway stabilizes and increases SMN mRNA levels leading to increased SMN protein levels. In this report, we explore the impact of the p38 activating, FDA-approved, blood brain barrier permeating compound celecoxib on SMN levels in vitro and in a mouse model of SMA. We demonstrate a significant induction of SMN protein levels in human and mouse neuronal cells upon treatment with celecoxib. We show that activation of the p38 pathway by low doses celecoxib increases SMN protein in a HuR protein-dependent manner. Furthermore, celecoxib treatment induces SMN expression in brain and spinal cord samples of wild-type mice in vivo. Critically, celecoxib treatment increased SMN levels, improved motor function and enhanced survival in a severe SMA mouse model. Our results identify low dose celecoxib as a potential new member of the SMA therapeutic armamentarium.

Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

PubMed

Maganji, Manisha; Connolly, Mark P; Bhatt, Aomesh

2018-01-01

Ibuprofen is a commonly used non-steroidal anti-inflammatory drug administered to treat injuries, joint pain, and recurrent muscular skeletal pain. The aim of this study was to determine the cutaneous irritancy of a medicated ibuprofen plaster compared with a placebo plaster in healthy volunteers. Healthy volunteers (N = 31) were treated at the same time with one ibuprofen and one placebo plaster. The ibuprofen and placebo plaster were applied in a randomized fashion to sites on the left or right side of subjects' lower backs. At each scheduled visit, the plasters and applications sites were assessed for degree of adhesion and skin irritancy, respectively. The plasters were applied on study Days 1, 2, 3, 5, 8, 10, 12, 15, 17, and 19, with final plaster removal on Day 22. The ibuprofen medicated plaster compared with placebo had a lower percentage of Grade 1 (23.3% vs. 46.7%, respectively), Grade 2 (10% vs. 20%), and ≥Grade 3 (3% vs. 16.1%) irritancy scores after 21 days of application. The mean irritation score across the study was 0.40 for the ibuprofen medicated plaster and 1.18 for the placebo plaster. The irritation score on Day 22 of the study was 0.53 for the ibuprofen medicated plaster and 1.50 for placebo. The placebo plaster was associated with a higher number of stopped applications due to Grade 3 or above skin reactions compared with the ibuprofen medicated plaster (5 vs. 1, respectively). The ibuprofen medicated plaster was well tolerated and was associated with lower irritancy than the placebo plaster.

Formulation studies on ibuprofen sodium-cationic dextran conjugate: effect on tableting and dissolution characteristics of ibuprofen.

PubMed

Abioye, Amos Olusegun; Kola-Mustapha, Adeola

2016-01-01

The effect of electrostatic interaction between ibuprofen sodium (IbS) and cationic diethylaminoethyl dextran (Ddex), on the tableting properties and ibuprofen release from the conjugate tablet was investigated. Ibuprofen exhibits poor flow, compaction (tableting) and dissolution behavior due to its hydrophobic structure, high cohesive, adhesive and viscoelastic properties therefore it was granulated with cationic Ddex to improve its compression and dissolution characteristics. Electrostatic interaction and hydrogen bonding between IbS and Ddex was confirmed with FT-IR and DSC results showed a stepwise endothermic solid-solid structural transformation from racemic to anhydrous forms between 120 and 175 °C which melted into liquid form at 208.15 °C. The broad and diffused DSC peaks of the conjugate granules as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. It was evident that Ddex improved the flowability and densification of the granules and increased the mechanical and tensile strengths of the resulting tablets as the tensile strength increased from 0.67 ± 0.0172 to 1.90 ± 0.0038 MPa with increasing Ddex concentration. Both tapping and compression processes showed that the most prominent mechanism of densification were particle slippage, rearrangement and plastic deformation while fragmentation was minimized. Ddex retarded the extent of dissolution in general, indicating potentials for controlled release formulations. Multiple release mechanisms including diffusion; anomalous transport and super case II transport were noted. It was concluded that interaction between ibuprofen sodium and Ddex produced a novel formulation with improved flowability, tableting and dissolution characteristics with potential controlled drug release characteristics dictated by Ddex concentration.

Celecoxib and octreotide synergistically ameliorate portal hypertension via inhibition of angiogenesis in cirrhotic rats.

PubMed

Gao, Jin-Hang; Wen, Shi-Lei; Feng, Shi; Yang, Wen-Juan; Lu, Yao-Yao; Tong, Huan; Liu, Rui; Tang, Shi-Hang; Huang, Zhi-Yin; Tang, Ying-Mei; Yang, Jin-Hui; Xie, Hui-Qi; Tang, Cheng-Wei

2016-10-01

Abnormal angiogenesis is critical for portal hypertension in cirrhosis. Except for etiological treatment, no efficient medication or regime has been explored to treat the early stage of cirrhosis when angiogenesis is initiated or overwhelming. In this study, we explored an anti-angiogenesis effort through non-cytotoxic drugs octreotide and celecoxib to treat early stage of cirrhotic portal hypertension in an animal model. Peritoneal injection of thioacetamide (TAA) was employed to induce liver cirrhosis in rats. A combination treatment of celecoxib and octreotide was found to relieve liver fibrosis, portal venous pressure, micro-hepatic arterioportal fistulas, intrahepatic and splanchnic angiogenesis. Celecoxib and octreotide exerted their anti-angiogenesis effect via an axis of cyclooxygenase-2/prostaglandin E2/EP-2/somatostatin receptor-2, which consequently down-regulated phosphorylation of extracellular signal-regulated kinase (p-ERK)-hypoxia-inducible factor-1α (HIF-1α)-vascular endothelial growth factor (VEGF) integrated signaling pathways. In conclusions, combination of celecoxib and octreotide synergistically ameliorated liver fibrosis and portal hypertension of the cirrhotic rats induced by TAA via the inhibition of intrahepatic and extrahepatic angiogenesis. The potential mechanisms behind the regimen may due to the inactivation of p-ERK-HIF-1α-VEGF signaling pathway.

Drug interaction between celecoxib and methotrexate in organic anion transporter 3-transfected renal cells and in rats in vivo.

PubMed

Maeda, Akimitsu; Tsuruoka, Shuichi; Ushijima, Kentarou; Kanai, Yoshikatsu; Endou, Hitoshi; Saito, Kazuyuki; Miyamoto, Etsuko; Fujimura, Akio

2010-08-25

Methotrexate has a clinically important pharmacokinetic interaction with nonsteroidal anti-inflammatory drugs (NSAIDs) mainly through its competition for tubular secretion via the renal organic anion transporter 3 (OAT3). We have previously reported the usefulness of OAT3-transfected renal tubular cells for screening of the drugs which interfere with the pharmacokinetics of methotrexate. Celecoxib, a cyclooxygenase (COX) 2 inhibitor, has not been reported to interact with methotrexate, but the mechanisms are unclear why the interaction did not occur. The purpose of this study was to evaluate the effect of celecoxib on methotrexate tubular secretion using a renal cell line stably expressing human OAT3 (S2-hOAT3), and to evaluate the pharmacokinetic interaction of the two drugs in rats. [3H]methotrexate uptake into S2-hOAT3 cells was significantly inhibited by celecoxib in a concentration-dependent manner and the Ki value was 35.3 microM. However, methotrexate serum concentrations and urinary excretion of methotrexate over 24 h in rats were not affected by celecoxib (50, 200 mg/kg). Celecoxib serum concentrations were increased by the increase in celecoxib dosage and the maximum drug concentration (Cmax) was 20.6 microM (celecoxib 200 mg/kg), which did not reach the Ki value obtained in the in vitro study. These results indicated that celecoxib inhibited the secretion of methotrexate via hOAT3, which suggested that celecoxib was a substrate of hOAT3. However, co-administration of the two drugs at clinical dosage did not affect the pharmacokinetics of methotrexate, because the serum concentrations did not reach the Ki value. Although the accumulation study using S2-hOAT3 cells was useful to predict the interaction between the new drug and methotrexate in vivo, a comparison of the Ki value with the Cmax in clinical dosage was necessary to evaluate the degree of this interaction. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Effect of Ibuprofen on masking endodontic diagnosis.

PubMed

Read, Jason K; McClanahan, Scott B; Khan, Asma A; Lunos, Scott; Bowles, Walter R

2014-08-01

An accurate diagnosis is of upmost importance before initiating endodontic treatment; yet, there are occasions when the practitioner cannot reproduce the patient's chief complaint because the patient has become asymptomatic. Ibuprofen taken beforehand may "mask" or eliminate the patient's symptoms. In fact, 64%-83% of patients with dental pain take analgesics before seeing a dentist. The purpose of this study was to examine the possible "masking" effect of ibuprofen on endodontic diagnostic tests. Forty-two patients with endodontic pain underwent testing (cold, percussion, palpation, and bite force measurement) and then received either placebo or 800 mg ibuprofen. Both patients and operators were blinded to the medication received. One hour later, diagnostic testing was repeated and compared with pretreatment testing. Ibuprofen affected testing values for vital teeth by masking palpation 40%, percussion 25%, and cold 25% on affected teeth with symptomatic irreversible pulpitis and symptomatic apical periodontitis. There was no observed masking effect in the placebo group on palpation, percussion, or cold values. When nonvital teeth were included, the masking effect of ibuprofen was decreased. However, little masking occurred with the bite force measurement differences. Analgesics taken before the dental appointment can affect endodontic diagnostic testing results. Bite force measurements can assist in identifying the offending tooth in cases in which analgesics "mask" the endodontic diagnosis. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Efficacy of adjunctive celecoxib treatment for patients with major depressive disorder: a meta-analysis.

PubMed

Na, Kyoung-Sae; Lee, Kang Joon; Lee, Ji Sung; Cho, Young Sung; Jung, Han-Yong

2014-01-03

Numerous studies have reported that inflammation is closely associated with depression, and adjunctive non-steroidal anti-inflammatory drug (NSAID) treatment has been suggested as a novel therapeutic approach for depression. We searched electronic databases including Medline, Embase, and the Cochrane Central Register of Controlled Trials. We only included randomized controlled trials comparing adjunctive NSAIDs with placebos for treating depressive episodes. Of the 654 retrieved entries, we identified four relevant studies with a total of 150 patients (75 NSAID patients and 75 placebo patients) with depressive episodes. All four studies used celecoxib as the NSAID. The patients receiving adjunctive celecoxib had significantly higher mean changes in the Hamilton Rating Scale for Depression scores between baseline and endpoint measurements compared with those receiving placebo (weighted mean difference=3.26, 95% confidence interval; CI=1.81 to 4.71). The adjunctive celecoxib group also showed better remission (odds ratio; OR=6.58, 95% CI=2.55 to 17.00) and response rates (OR=6.49, 95% CI=2.89 to 14.55) than the placebo group. The all-cause drop-out rate was more favorable for the celecoxib group than for the placebo group (OR=0.45, 95% CI=0.18 to 1.13), although the statistical significance was not statistically significant (p=0.09). Adjunctive treatment with NSAIDs, particularly celecoxib, can be a promising strategy for patients with depressive disorder. Future studies with a larger sample size and longer study duration are needed to confirm the efficacy and tolerability of NSAIDs for depression. © 2013.

[Effects of perioperative administration of celecoxib on pain management and recovery of function after total knee replacement].

PubMed

Shen, Bin; Tang, Xin; Yang, Jing; Li, Yong; Zhou, Zong-ke; Kang, Peng-de; Pei, Fu-xing

2009-01-15

To assess the effect of perioperative administration of a selective cyclooxygenase 2 inhibitor (celecoxib) on pain management and recovery of function after total knee arthroplasty (TKA). Randomized, controlled trial conducted from January 2005 through February 2006, 60 patients underwent TKA for osteoarthritis or rheumatoid arthritis were randomly divided into group of perioperative, administration of celecoxib (Study group, n = 30) and postoperative administration of celecoxib (Control group, n = 30). Patients in Study group were given oral celecoxib 3 d before TKA, 200 mg twice daily, and extended to 5 d postoperatively; patients in Control group were given oral celecoxib 2 h after TKA, 200 mg twice daily, and extended to 5 d postoperatively. All operations were finished by the same surgeon group. The postoperative patient-controlled analgesia (PCA) consumption was significantly less in Study group than in Control group [(43 +/- 12) ml vs. (53 +/- 12) ml, P < 0.05]. The pain scores of postoperative 4, 8, 12 h, 1, 2 d in Study group were 6.1 +/- 1.2, 5.0 +/- 1.3, 4.3 +/- 1.1, 3.4 +/- 1.2, significantly less than in Control group (P < 0.05); There were no intergroup significant differences in the pain scores of postoperative 3, 4, 5 d (P > 0.05). There were no intergroup significant differences in respect to the side-effect occurrence, operation time and postoperative drainage, postoperative analgesic consumption (P > 0.05). The time to achieve 90 degrees knee flexion was significantly shorter in Study group than in Control group [(6.2 +/- 1.7) d vs. (8.6 +/- 1.8) d, P < 0.05]. Perioperative administration of the selective Celecoxib holds the effect of preemptive analgesia. Compared with postoperative administration, perioperative administration of celecoxib can alleviate the early postoperative pain score, reduce the consumption of postoperative analgesic, accelerate the recovery of joint motion and thus increase the patient satisfaction.

Ibuprofen does not reverse ventilatory acclimatization to chronic hypoxia.

PubMed

De La Zerda, D J; Stokes, J A; Do, J; Go, A; Fu, Z; Powell, F L

2017-07-27

Ventilatory acclimatization to hypoxia involves an increase in the acute hypoxic ventilatory response that is blocked by non-steroidal anti-inflammatory drugs administered during sustained hypoxia. We tested the hypothesis that inflammatory signals are necessary to sustain ventilatory acclimatization to hypoxia once it is established. Adult, rats were acclimatized to normoxia or chronic hypoxia (CH, [Formula: see text] =70Torr) for 11-12days and treated with ibuprofen or saline for the last 2days of hypoxia. Ventilation, metabolic rate, and arterial blood gas responses to O 2 and CO 2 were not affected by ibuprofen after acclimatization had been established. Immunohistochemistry and image analysis showed acute (1h) hypoxia activated microglia in a medullary respiratory center (nucleus tractus solitarius, NTS) and this was blocked by ibuprofen administered from the beginning of hypoxic exposure. Microglia returned to the control state after 7days of CH and were not affected by ibuprofen administered for 2 more days of CH. In contrast, NTS astrocytes were activated by CH but not acute hypoxia and activation was not reversed by administering ibuprofen for the last 2days of CH. Hence, ibuprofen cannot reverse ventilatory acclimatization or astrocyte activation after they have been established by sustained hypoxia. The results are consistent with a model for microglia activation or other ibuprofen-sensitive processes being necessary for the induction but not maintenance of ventilatory acclimatization to hypoxia. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose.

PubMed

Baek, Hyung Hee; Kim, Dae-Hwan; Kwon, So Young; Rho, Shin-Joung; Kim, Dong-Wuk; Choi, Han-Gon; Kim, Yong-Ro; Yong, Chul Soon

2012-03-01

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose, it was prepared using spray-drying techniques with cycloamylose at a weight ratio of 1:1. The effect of cycloamylose on aqueous solubility of ibuprofen was investigated. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared with ibuprofen powder. This ibuprofen-loaded solid dispersion improved about 14-fold drug solubility. Ibuprofen was present in an unchanged crystalline state, and cycloamylose played the simple role of a solubilizing agent in this solid dispersion. Moreover, the dispersion gave 2-fold higher AUC (area under the drug concentration-time curve) value compared with a ibuprofen powder, indicating that it improved the oral bioavailability of ibuprofen in rats. Thus, the solid dispersion may be useful to deliver ibuprofen with enhanced bioavailability without crystalline change.

Use of ibuprofen and risk of Parkinson disease

PubMed Central

Chen, Honglei; Schwarzschild, Michael A.; Ascherio, Alberto

2011-01-01

Background: Neuroinflammation may contribute to the pathogenesis of Parkinson disease (PD). Use of nonsteroidal anti-inflammatory drugs (NSAID) in general, and possibly ibuprofen in particular, has been shown to be related to lower PD risk in previous epidemiologic studies. Methods: We prospectively examined whether use of ibuprofen or other NSAIDs is associated with lower PD risk among 136,197 participants in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) free of PD at baseline (1998 for NHS and 2000 for HPFS). NSAIDs use was assessed via questionnaire. Results were combined in a meta-analysis with those of published prospective investigations. Results: We identified 291 incident PD cases during 6 years of follow-up. Users of ibuprofen had a significantly lower PD risk than nonusers (relative risk [RR], adjusted for age, smoking, caffeine, and other covariates = 0.62; 95% confidence interval [CI] 0.42–0.93; p = 0.02). There was a dose–response relationship between tablets of ibuprofen taken per week and PD risk (p trend = 0.01). In contrast, PD risk was not significantly related to use of aspirin (RR = 0.99; 95% CI 0.78–1.26), other NSAIDs (RR = 1.26; 95% CI 0.86–1.84), or acetaminophen (RR = 0.86; 95% CI 0.62–1.18). Similar results were obtained in the meta-analyses: the pooled RR was 0.73 (95% CI 0.63–0.85; p < 0.0001) for ibuprofen use, whereas use of other types of analgesics was not associated with lower PD risk. Conclusions: The association between use of ibuprofen and lower PD risks, not shared by other NSAIDs or acetaminophen, suggests ibuprofen should be further investigated as a potential neuroprotective agent against PD. PMID:21368281

Celecoxib, a specific COX-2 inhibitor, has no significant effect on methotrexate pharmacokinetics in patients with rheumatoid arthritis.

PubMed

Karim, A; Tolbert, D S; Hunt, T L; Hubbard, R C; Harper, K M; Geis, G S

1999-12-01

To determine the effects of celecoxib, a specific inhibitor of cyclooxygenase 2 (COX-2) on the renal clearance and plasma pharmacokinetic profile of stable methotrexate (MTX) doses in patients with rheumatoid arthritis (RA). Fourteen adult female patients with RA taking a stable weekly dose of MTX (5 to 15 mg/wk) for a minimum of 3 months were randomized to receive concomitantly either celecoxib (200 mg BID) or placebo for a period of 7 days in a single blind, 2 period crossover study of MTX pharmacokinetics and renal clearance. The plasma pharmacokinetic profile of MTX did not change significantly when celecoxib or a placebo was coadministered. The mean renal clearance of MTX alone, 7.98+/-2.18 l/h, was virtually unchanged by coadministration of celecoxib (7.94+/-1.61 l/h) or placebo (7.97+/-1.19 l/h). Celecoxib has no significant effect on the pharmacokinetics or renal clearance of MTX in patients with RA, although these results should be confirmed in prospective studies of elderly and renally impaired patients.

Loxoprofen sodium and celecoxib for postoperative pain in patients after spinal surgery: a randomized comparative study.

PubMed

Sekiguchi, Hiroyuki; Inoue, Gen; Nakazawa, Toshiyuki; Imura, Takayuki; Saito, Wataru; Uchida, Kentaro; Miyagi, Masayuki; Takahira, Naonobu; Takaso, Masashi

2015-07-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are often used to treat inflammation, pain, and fever, but no criterion standard exists for the management of postoperative pain following spinal surgery. In the present study, we compared the analgesic efficacy of loxoprofen sodium (loxoprofen) and celecoxib for the management of postoperative pain following spinal surgery. One-hundred forty-one patients (mean age 62.2 years) were randomly assigned to two groups before spinal surgery: a loxoprofen group (n = 73, 180 mg/day) and a celecoxib group (n = 68, 200 mg/day). The drugs were administered from 1 day until 7 days after surgery. A numeric rating scale (NRS) was used to evaluate pain at nine predefined times every day and the findings were compared between the two groups. Laboratory data and adverse events were also recorded. There was no significant difference in the maximum and mean NRS scores on each day between loxoprofen and celecoxib, suggesting a comparable analgesic effect for these two NSAIDs. Greater improvement in the NRS score between preadministration (baseline) and 30 min or 2 h after administration was obtained for loxoprofen. This tendency was shown for both slight (NRS score <5 at baseline) and severe pain (NRS score ≥ 5 at baseline). Loxoprofen was discontinued in one patient on day 4 because of renal dysfunction. Celecoxib was discontinued in one patient on day 2 at the patient's request. Both loxoprofen sodium and celecoxib were well tolerated for the relief of acute postoperative pain after spinal surgery. A single administration of loxoprofen showed superior and rapid effectiveness compared with celecoxib for both slight and severe postoperative pain.

Managing Osteoarthritis Pain with Medicines: A Review of the Research for Adults

MedlinePlus

... much you buy at one time. When you shop around for the best price, you should also consider the quality of the product. 7 Wholesale Prices of Prescription Analgesics Drug Name NSAIDs Celecoxib Ibuprofen Diclofenac Naproxen Etodolac Meloxicam ...

Efficacy of celecoxib in the treatment of CNS lymphomas: an in vivo model.

PubMed

Wang, Weijun; Kardosh, Adel; Su, Yuzhuang S; Schonthal, Axel H; Chen, Thomas C

2006-11-15

The incidence of primary central nervous system lymphomas (PCNSLs) has increased over the past several decades. Unfortunately, even with the most effective therapeutic regimen (that is, methotrexate with wholebrain radiation therapy), PCNSL recurs within a few years in more than half of the treated patients and is eventually fatal. Because PCNSL usually occurs in older patients and in those with acquired immunodeficiency syndrome, combination treatments in which both chemo- and radiation therapy are used is often poorly tolerated and results in a significant reduction in the quality of life. Recently, it has been demonstrated that the selective cyclooxygenase- 2 inhibitor celecoxib (Celebrex), can block the growth of lymphoma cells in vitro. To create an experimental animal model in vivo for the PCNSL study, the authors intracranially injected a human B-cell lymphoma cell line into nude mice. Their data demonstrate that this experimental model is an excellent one for human PCNSL with brain and leptomeningeal involvement. They also evaluated the feasibility of using celecoxib as a therapeutic agent in the treatment of PCNSL. Nude mice with intracranial lymphomas were treated with celecoxib contained in the animal chow. The treated animals demonstrated significantly prolonged survival times compared with the untreated animals. Based on the authors' data, celecoxib may be a promising therapeutic agent for the treatment of PCNSL.

Acute pain management: acetaminophen and ibuprofen are often under-dosed.

PubMed

Milani, Gregorio P; Benini, Franca; Dell'Era, Laura; Silvagni, Davide; Podestà, Alberto F; Mancusi, Rossella Letizia; Fossali, Emilio F

2017-07-01

Most children with pain are managed by either acetaminophen or ibuprofen. However, no study has so far investigated if children are prescribed adequate doses of acetaminophen or ibuprofen in emergency department. Aim of this retrospective study was to investigate the prevalence of under-dosage of these drugs in children presenting with pain in emergency department. Children initially prescribed with acetaminophen or ibuprofen for pain management were included. The χ 2 automatic interaction detection method was used considering the percentage variation from the minimum of the appropriate dose as dependent variable while prescribed drug, age, gender, body weight, type of hospital (pediatric or general), and availability of internal guidelines on pediatric pain management in the emergency department as independent variables. Data on 1471 children managed for pain were available. Under-dosage was prescribed in 893 subjects (61%), of whom 577 were prescribed acetaminophen and 316 ibuprofen. The use of acetaminophen suppositories, body weight <12 kg or >40 kg, and the use of oral ibuprofen identified clusters of children associated with under-dosage prescription. Prescription of acetaminophen and ibuprofen was frequently under-dosed. The use of suppositories, lower and higher body weight, and the use of ibuprofen were associated with under-dosage. Under-dosing may reflect prescription of anti-pyretic doses. Agenzia Italiana del Farmaco-Observational Study Register (RSO). Registration code: PIERRE/1 What is Known: • Pain is frequent in children presented to emergency department. • International recommendations on pain management are often not implemented. What is New: • Acetaminophen and ibuprofen were frequently underdosed in children prescribed for pain in the Italian emergency departments. • Under-dosage may be related to the habit of using acetaminophen and ibuprofen in the recommended range for fever treatment.

ZD6474, a new treatment strategy for human osteosarcoma, and its potential synergistic effect with celecoxib

PubMed Central

Pan, Changchuan; Zhou, Yi; Du, Wuying; Chen, Jie-min; Zhu, Xiaofeng; Shen, Jingnan; Chen, Shuai; Liu, Ran-yi; Huang, Wenlin

2015-01-01

ZD6474, a small molecule VEGFR and EGFR tyrosine kinase inhibitor, has been considered as a promising tumor-targeted drug in various malignancies. EGFR and cyclooxygenase-2 (COX-2) were found overexpressed in osteosarcoma in previous reports, so here we tried to explore the anti-osteosarcoma effect of ZD6474 alone or combination with celecoxib, a COX-2 inhibitor. The data demonstrated that ZD6474 inhibited the growth of osteosarcoma cells, and promoted G1-phase cell cycle arrest and apoptosis by inhibiting the activity of EGFR tyrosine kinase, and consequently suppressing its downstream PI3k/Akt and MAPK/ERK pathway. Additionally, daily administration of ZD6474 produced a dose-dependent inhibition of tumor growth in nude mice. Celecoxib also significantly inhibited the growth of osteosarcoma cells in dose-dependent manner, while combination of ZD6474 and celecoxib displayed a synergistic or additive antitumor effect on osteosarcoma in vitro and in vivo. The possible molecular mechanisms to address the synergism are likely that ZD6474 induces the down-regulation of COX-2 expression through inhibiting ERK phosphorylation, while celecoxib promotes ZD6474-directed inhibition of ERK phosphorylation. In conclusion, ZD6474 exerts direct anti-proliferative effects on osteosarcoma cells, and the synergistic antitumor effect of the combination of ZD6474 with celecoxib may indicate a new strategy of the combinative treatment of human osteosarcoma. PMID:26050198

Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis.

PubMed

Tellegen, A R; Rudnik-Jansen, I; Pouran, B; de Visser, H M; Weinans, H H; Thomas, R E; Kik, M J L; Grinwis, G C M; Thies, J C; Woike, N; Mihov, G; Emans, P J; Meij, B P; Creemers, L B; Tryfonidou, M A

2018-11-01

Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n = 6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39 mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6 days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.

pH dependent conjugation of Ibuprofen to PEGylated nanoparticles

NASA Astrophysics Data System (ADS)

Bharti, Shivani; Jain, Shikshita; Kaur, Gurvir; Gupta, Shikha; Tripathi, S. K.

2018-04-01

In this paper, Ibuprofen, a water insoluble drug was covalently attached to PEGylated nanoparticles. Firstly, Surface functionalization of water dispersed core/shell nanoparticles had been done using hydrophilic polymer PEG-diamine. Therefore, PEGylated nanoparticles contain NH2 groups over the surface of nanoparticles and can be used for the further attachment of biomolecules. Ibuprofen was covalently loaded on the PEGylated core/shell nanoparticles using carbodiimide reaction. The synthesis had been carried out under two different pH environments, as the solubility of Ibuprofen is pH dependent. The resultant samples were characterized using UV-Vis absorption and FT-IR spectroscopy. The results strongly suggest the successful chemical conjugation of Ibuprofen to PEGylated nanoparticles in aqueous media and they could be further used for drug delivery applications.

Fulvic Acid Mediated Photolysis of Ibuprofen in Water.

EPA Science Inventory

Photolysis of the nonsteroidal anti-inflammatory drug ibuprofen was studied in solutions of fulvic acid (FA) isolated from Pony Lake, Antarctica; Suwannee River, GA, USA; and Old Woman Creek, OH, USA. At an initial concentration of 10 µM ibuprofen degrades by direct photolysis...

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer.

PubMed

Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M; Gehrig, Paola A; Zhou, Chunxiao; Bae-Jump, Victoria L

2016-06-28

Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women.

The effect of celecoxib on tumor growth in ovarian cancer cells and a genetically engineered mouse model of serous ovarian cancer

PubMed Central

Suri, Anuj; Sheng, Xiugui; Schuler, Kevin M.; Zhong, Yan; Han, Xiaoyun; Jones, Hannah M.; Gehrig, Paola A.; Zhou, Chunxiao; Bae-Jump, Victoria L.

2016-01-01

Our objective was to evaluate the effect of the COX-2 inhibitor, celecoxib, on (1) proliferation and apoptosis in human ovarian cancer cell lines and primary cultures of ovarian cancer cells, and (2) inhibition of tumor growth in a genetically engineered mouse model of serous ovarian cancer under obese and non-obese conditions. Celecoxib inhibited cell proliferation in three ovarian cancer cell lines and five primary cultures of human ovarian cancer after 72 hours of exposure. Treatment with celecoxib resulted in G1 cell cycle arrest, induction of apoptosis, inhibition of cellular adhesion and invasion and reduction of expression of hTERT mRNA and COX-2 protein in all of the ovarian cancer cell lines. In the KpB mice fed a high fat diet (obese) and treated with celecoxib, tumor weight decreased by 66% when compared with control animals. Among KpB mice fed a low fat diet (non-obese), tumor weight decreased by 46% after treatment with celecoxib. In the ovarian tumors from obese and non-obese KpB mice, treatment with celecoxib as compared to control resulted in decreased proliferation, increased apoptosis and reduced COX-2 and MMP9 protein expression, as assessed by immunohistochemistry. Celecoxib strongly decreased the serum level of VEGF and blood vessel density in the tumors from the KpB ovarian cancer mouse model under obese and non-obese conditions. This work suggests that celecoxib may be a novel chemotherapeutic agent for ovarian cancer prevention and treatment and be potentially beneficial in both obese and non-obese women. PMID:27074576

Stimulus specific effect of ibuprofen on chemiluminescence of sheep neutrophils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tahamont, M.V.; Margiotta, M.; Gee, M.H.

1986-03-05

The authors have shown that pretreatment with ibuprofen inhibits free radical release from complement stimulated neutrophils. To further examine the effect of ibuprofen on neutrophil free radical release, they stimulated neutrophils with the synthetic peptide, FMLP, phorbol myristate acetate (PMA), or zymosan-activated plasma (ZAP). Pure (>95%), viable (>95%) sheep neutrophils (2 x 10/sup 6/) were placed in HEPES buffer, luminol, drug or vehicle and stimulated in the luminometer with one of the stimuli. The chemiluminescence (CL) response was recorded and the drug treated samples were compared to vehicle treated controls. Ibuprofen had a dose dependent effect on CL in ZAPmore » stimulated neutrophils. At the highest dose (10/sup -2/M) these cells produced only 37 +/- 7% of the CL response observed in the control cells. In contrast, at the same dose, ibuprofen did not significantly attenuate CL seen in FMLP stimulated cells, with these cells producing 79 +/- 7% of the control cells; nor did ibuprofen effect PMA stimulated CL, as these cells produced a CL response that was 85 +/- 8% of the control cells. Ibuprofen appears to have a stimulus specific effect on free radical release in activated neutrophils. It is also apparent that ibuprofen inhibits complement stimulated free radical release by some mechanism independent of its cyclooxygenase inhibitory effect.« less

Celecoxib enhances the radiosensitivity of HCT116 cells in a COX-2 independent manner by up-regulating BCCIP

PubMed Central

Xu, Xiao-Ting; Hu, Wen-Tao; Zhou, Ju-Ying; Tu, Yu

2017-01-01

It has been reported that celecoxib, a cyclooxygenase-2 (COX-2)-selective nonsteroidal anti-inflammatory drug (NSAID), regulates the radiosensitivity of several cancer cells. BCCIP (BRCA2 and CDKN1A interacting protein) plays a critical role in maintaining the critical functions of p53 in tumor suppression and response to therapy. However, whether the effect of celecoxib on the radiosensitivity of colorectal cancer (CRC) cells is dependent on BCCIP is largely unclear. In this study, we found that celecoxib enhanced the radiosensitivity of HeLa (a human cervical carcinoma cell line), A549 (a human lung carcinoma cell line), and HCT116 cells (a human CRC cells line). Among these cells, COX-2 expression was undetected in HCT116 cells. Treatment with celecoxib significantly increased BCCIP expression in COX-2 negative HCT116 cells. Knockdown of BCCIP obviously abrogated the enhanced radiosensitivity of HCT116 cells induced by celecoxib. A combination of celecoxib and irradiation treatment induced much more γ-H2AX foci formation, higher levels of radiation injury-related proteins phosphorylation, G2/M arrest, apoptosis, and p53 and p21 expression, and lower levels of Cyclin B1 in HCT116 cells than those in cells treated with irradiation alone. However, these changes were undetected in BCCIP-silenced HCT116 cells. Therefore, these data suggest that BCCIP gene may be a radiosensitivity-related gene in CRC. Celecoxib affects the functions of p53 and inhibits the recovery from the irradiation-induced injury by up-regulating the expression of BCCIP, and subsequently regulates the expressions of genes such as p21 and Cyclin B1 to enhance the radiosensitivity of HCT116 cells in a COX-2 independent manner. PMID:28386336

Ibuprofen partially attenuates neurodegenerative symptoms in presenilin conditional double-knockout mice.

PubMed

Dong, Z; Yan, L; Huang, G; Zhang, L; Mei, B; Meng, B

2014-06-13

Ibuprofen is a widely used nonsteroidal anti-inflammatory drug that reportedly reduces the risk of Alzheimer's disease (AD) development. The anti-inflammatory effect of ibuprofen occurred via inhibition of cyclooxygenases and anti-amyloidogenesis through modulation of γ-secretase. Presenilin 1 and 2 conditional double-knockout (cDKO) mice exhibited age-dependent memory impairment and forebrain degeneration without elevation of amyloid β deposition. Therefore, cDKO mice can be an ideal animal model on which to independently test the effects of ibuprofen anti-inflammatory properties on the prevention of AD. Three- and six-month-old cDKO mice were fed diet containing 375 ppm ibuprofen for six months. After multiple, well-validated behavioral tests, treatment with ibuprofen improved cognition-related behavioral performance, and drug efficacy was correlated with the timing of administration. Ibuprofen was more effective on six-month-old than on three-month-old cDKO mice. Biochemical analysis demonstrated that the effects of ibuprofen on glial fibrillary acidic protein and CD68 expression levels were uneven in different brain regions of cDKO mice and that age also influenced such effects. Tau hyperphosphorylation and the cleavage of caspase-3 decreased after ibuprofen treatment, and this effect was more significant in the older than the younger group of mice, which was consistent with the results of behavioral tests. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Celecoxib activates PI-3K/Akt and mitochondrial redox signaling to enhance heme oxygenase-1-mediated anti-inflammatory activity in vascular endothelium.

PubMed

Hamdulay, Shahir S; Wang, Bufei; Birdsey, Graeme M; Ali, Faisal; Dumont, Odile; Evans, Paul C; Haskard, Dorian O; Wheeler-Jones, Caroline P; Mason, Justin C

2010-04-15

Although nonsteroidal anti-inflammatory drugs (NSAIDs) provide important control of pain and inflammation, they have been overshadowed by concerns regarding atherothrombotic complications. However, celecoxib seems to have a relatively good cardiovascular profile and may improve endothelial function in coronary heart disease. This led us to the hypothesis that celecoxib induces the vasculoprotective enzyme heme oxygenase-1 (HO-1). In human umbilical vein and aortic endothelial cells, 24-48 h treatment with celecoxib induced HO-1 mRNA and protein expression and increased HO-1 enzyme activity. This effect was not seen with rofecoxib or indomethacin. Supplementation of culture medium with iloprost or prostaglandin E(2) failed to reverse celecoxib-mediated HO-1 induction, indicating a cyclooxygenase-independent mechanism. Rather, this action of celecoxib involved generation of mitochondria-derived reactive oxygen species, Akt phosphorylation, and nuclear translocation of the transcription factor Nrf2, with N-acetylcysteine, PI-3K antagonist LY290042, and dominant-negative Akt abrogating the effects. Furthermore, celecoxib-induced HO-1 was inhibited by dominant-negative Nrf2. The functional significance of HO-1 induction was revealed by celecoxib-mediated inhibition of VCAM-1 expression, a response reversed by the HO-1 antagonist zinc protoporphyrin. HO-1 induction provides a molecular mechanism for clinical observations indicating relative freedom from atherothrombotic complications in patients taking celecoxib compared to other NSAIDs with comparable anti-inflammatory activity. Copyright 2010 Elsevier Inc. All rights reserved.

The effect of anti-rheumatic medications for coronary artery diseases risk in patients with rheumatoid arthritis might be changed over time: A nationwide population-based cohort study

PubMed Central

Lin, Lichi; Chen, Chyong-Mei; Chiou, Jeng-Yuan; Wang, Yu-Hsun; Wang, Paul Yung-Pou; Wei, James Cheng-Chung

2017-01-01

Objectives To determine whether anti-rheumatic drug usage is associated with risk of coronary artery diseases (CAD) in incident Rheumatoid Arthritis (RA) patients. Methods Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 6260 patients who were newly diagnosed with RA between 2001–2010. The study endpoint was occurrence of CAD according to the ICD-9-CM codes. We used the WHO Defined Daily Dose (DDD) as a tool to assess the drugs exposure. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) of disease after controlling for demographic and other co-morbidities. When the proportionality assumption is violated, a spline curve of the Scaled Schoenfeld residuals is fitted to demonstrate the estimated effect on CAD over time for drug usage. Results Among RA patients, use of celecoxib, and etoricoxib was associated with significantly decreased incidence of CAD. The adjusted HR(95% CI) of CAD for low-dose celecoxib (DDD≦1) and high-dose user were 0.47(0.34, 0.65) and 0.37(0.24, 0.58) during the 4 year follow-up time; however, it became 0.98(0.70, 1.37) and1.29(0.85, 1.95). Adjusted HR(95% CI) of CAD for etoricoxib users remained 0.47(0.26, 0.84). Conclusions This study revealed association of decreased CAD risk in RA patients taking 2 different kinds of COX-2i in comparison with nonusers. The effect might be changed over time, after about 4 years. PMID:28658301

Celecoxib Induced Tumor Cell Radiosensitization by Inhibiting Radiation Induced Nuclear EGFR Transport and DNA-Repair: A COX-2 Independent Mechanism

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dittmann, Klaus H.; Mayer, Claus; Ohneseit, Petra A.

2008-01-01

Purpose: The purpose of the study was to elucidate the molecular mechanisms mediating radiosensitization of human tumor cells by the selective cyclooxygenase (COX)-2 inhibitor celecoxib. Methods and Materials: Experiments were performed using bronchial carcinoma cells A549, transformed fibroblasts HH4dd, the FaDu head-and-neck tumor cells, the colon carcinoma cells HCT116, and normal fibroblasts HSF7. Effects of celecoxib treatment were assessed by clonogenic cell survival, Western analysis, and quantification of residual DNA damage by {gamma}H{sub 2}AX foci assay. Results: Celecoxib treatment resulted in a pronounced radiosensitization of A549, HCT116, and HSF7 cells, whereas FaDu and HH4dd cells were not radiosensitized. The observedmore » radiosensitization could neither be correlated with basal COX-2 expression pattern nor with basal production of prostaglandin E2, but was depended on the ability of celecoxib to inhibit basal and radiation-induced nuclear transport of epidermal growth factor receptor (EGFR). The nuclear EGFR transport was strongly inhibited in A549-, HSF7-, and COX-2-deficient HCT116 cells, which were radiosensitized, but not in FaDu and HH4dd cells, which resisted celecoxib-induced radiosensitization. Celecoxib inhibited radiation-induced DNA-PK activation in A549, HSF7, and HCT116 cells, but not in FaDu and HH4dd cells. Consequentially, celecoxib increased residual {gamma}H2AX foci after irradiation, demonstrating that inhibition of DNA repair has occurred in responsive A549, HCT116, and HSF7 cells only. Conclusions: Celecoxib enhanced radiosensitivity by inhibition of EGFR-mediated mechanisms of radioresistance, a signaling that was independent of COX-2 activity. This novel observation may have therapeutic implications such that COX-2 inhibitors may improve therapeutic efficacy of radiation even in patients whose tumor radioresistance is not dependent on COX-2.« less

Celecoxib and tauro-ursodeoxycholic acid co-treatment inhibits cell growth in familial adenomatous polyposis derived LT97 colon adenoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heumen, Bjorn W.H. van, E-mail: b.vanheumen@mdl.umcn.nl; Roelofs, Hennie M.J.; Morsche, Rene H.M. te

Chemoprevention would be a desirable strategy to avoid duodenectomy in patients with familial adenomatous polyposis (FAP) suffering from duodenal adenomatosis. We investigated the in vitro effects on cell proliferation, apoptosis, and COX-2 expression of the potential chemopreventives celecoxib and tauro-ursodeoxycholic acid (UDCA). HT-29 colon cancer cells and LT97 colorectal micro-adenoma cells derived from a patient with FAP, were exposed to low dose celecoxib and UDCA alone or in combination with tauro-cholic acid (CA) and tauro-chenodeoxycholic acid (CDCA), mimicking bile of FAP patients treated with UDCA. In HT-29 cells, co-treatment with low dose celecoxib and UDCA resulted in a decreased cellmore » growth (14-17%, p < 0.01). A more pronounced decrease (23-27%, p < 0.01) was observed in LT97 cells. Cell growth of HT-29 cells exposed to 'artificial bile' enriched with UDCA, was decreased (p < 0.001), either in the absence or presence of celecoxib. In LT97 cells incubated with 'artificial bile' enriched with UDCA, cell growth was decreased only in the presence of celecoxib (p < 0.05). No clear evidence was found for involvement of proliferating cell nuclear antigen, caspase-3, or COX-2 in the cellular processes leading to the observed changes in cell growth. In conclusion, co-treatment with low dose celecoxib and UDCA has growth inhibitory effects on colorectal adenoma cells derived from a patient with FAP, and further research on this combination as promising chemopreventive strategy is desired. -- Highlights: Black-Right-Pointing-Pointer Celecoxib and UDCA acid co-treatment decreases cell growth in colon tumor cells. Black-Right-Pointing-Pointer UDCA enriched 'artificial bile' decreases LT-97 cell growth only in presence of celecoxib. Black-Right-Pointing-Pointer PCNA, caspase-3, nor COX-2 seem to be involved in the observed changes in cell growth.« less

Ibuprofen and Pregnancy

MedlinePlus

... care provider may follow the status of your baby’s heart and amniotic fluid volume in the third trimester by ultrasound. You should be on the lowest dose needed to treat your ... When needed, it is given to infants at higher doses. Ibuprofen use by the mother ...

Chrysin alleviates testicular dysfunction in adjuvant arthritic rats via suppression of inflammation and apoptosis: Comparison with celecoxib

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darwish, Hebatallah A.; Arab, Hany H., E-mail: hany.arab@pharma.cu.edu.eg; Abdelsalam, Rania M.

Long standing rheumatoid arthritis (RA) is associated with testicular dysfunction and subfertility. Few studies have addressed the pathogenesis of testicular injury in RA and its modulation by effective agents. Thus, the current study aimed at evaluating the effects of two testosterone boosting agents; chrysin, a natural flavone and celecoxib, a selective COX-2 inhibitor, in testicular impairment in rats with adjuvant arthritis, an experimental model of RA. Chrysin (25 and 50 mg/kg) and celecoxib (5 mg/kg) were orally administered to Wistar rats once daily for 21 days starting 1 h before arthritis induction. Chrysin suppressed paw edema with comparable efficacy tomore » celecoxib. More important, chrysin, dose-dependently and celecoxib attenuated the testicular injury via reversing lowered gonadosomatic index and histopathologic alterations with preservation of spermatogenesis. Both agents upregulated steroidogenic acute regulatory (StAR) mRNA expression and serum testosterone with concomitant restoration of LH and FSH. Furthermore, they suppressed inflammation via abrogation of myeloperoxidase, TNF-α and protein expression of COX-2 and iNOS besides elevation of IL-10. Alleviation of the testicular impairment was accompanied with suppression of oxidative stress via lowering testicular lipid peroxides and nitric oxide. With respect to apoptosis, both agents downregulated FasL mRNA expression and caspase-3 activity in favor of cell survival. For the first time, these findings highlight the protective effects of chrysin and celecoxib against testicular dysfunction in experimental RA which were mediated via boosting testosterone in addition to attenuation of testicular inflammation, oxidative stress and apoptosis. Generally, the 50 mg/kg dose of chrysin exerted comparable protective actions to celecoxib. - Highlights: • Chrysin and celecoxib alleviated testicular suppression in adjuvant arthritis. • They attenuated histopathological damage and preserved

Solid-phase microextraction and chiral HPLC analysis of ibuprofen in urine.

PubMed

de Oliveira, Anderson Rodrigo Moraes; Cesarino, Evandro José; Bonato, Pierina Sueli

2005-04-25

A simple and rapid solid-phase microextraction method was developed for the enantioselective analysis of ibuprofen in urine. The sampling was made with a polydimethylsiloxane-divinylbenzene coated fiber immersed in the liquid sample. After desorptioning from the fiber, ibuprofen enantiomers were analyzed by HPLC using a Chiralpak AD-RH column and UV detection. The mobile phase was made of methanol-pH 3.0 phosphoric acid solution (75:25, v/v), at a flow rate of 0.45 mL/min. The mean recoveries of SPME were 19.8 and 19.1% for (-)-R-ibuprofen and (+)-(S)-ibuprofen, respectively. The method was linear at the range of 0.25-25 microg/mL. Within-day and between-day assay precision and accuracy were below 15% for both ibuprofen enantiomers at concentrations of 0.75, 7.5 and 20 microg/mL. The method was tested with urine quality control samples and human urine fractions after administration of 200 mg rac-ibuprofen.

Effect of celecoxib on the antihypertensive effect of losartan in a rat model of renovascular hypertension.

PubMed

Boshra, Vivian; El Wakeel, Gehan Abdel Hamid; Nader, Manar A

2011-02-01

Certain nonsteroidal anti-inflammatory drugs have been reported to elevate blood pressure in some hypertensive patients, who are either untreated or treated with antihypertensive agents. This study was undertaken to determine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on the antihypertensive effects of the angiotensin II type 1 receptor (AT1) antagonist, losartan potassium. We studied the effect of oral treatment with losartan (30 mg/kg), celecoxib (3 mg/kg), and their combination on the mean arterial blood pressure (MAP), plasma renin activity (PRA), and plasma prostaglandin E2 (PGE2) in male Sprague-Dawley rats with renovascular hypertension (RVH) induced by partial subdiaphragmatic aortic constriction. Treatment was continued for 7 days after aortic coarctation. Aortic coarctation led to significant increases in the MAP, PRA, and plasma PGE2. In RVH rats, losartan treatment caused a significant decrease of MAP with a significant increase in both plasma PGE2 and PRA. Celecoxib caused a nonsignificant change in MAP with a significant decrease in the raised levels of plasma PGE2 and PRA. Concomitant administration of celecoxib and losartan did not significantly affect the lowering effect of losartan on MAP with a subsequent significant decrease in the plasma PGE2 and PRA in RVH rats. Therefore, celecoxib could be used in renin-dependent hypertensive patients who receive losartan, without fear of a rise in their blood pressure.

Tramadol versus Celecoxib for reducing pain associated with outpatient hysteroscopy: a randomized double-blind placebo-controlled trial.

PubMed

Hassan, A; Wahba, A; Haggag, H

2016-01-01

Which is better, Tramadol or Celecoxib, in reducing pain associated with outpatient hysteroscopy? Both Tramadol and Celecoxib are effective in reducing pain associated with outpatient hysteroscopy but Celecoxib may be better tolerated. Pain is the most common cause of failure of outpatient hysteroscopy. A systematic review and meta-analysis showed that local anaesthetics were effective in reducing pain associated with hysteroscopy but there was insufficient evidence to support the use of oral analgesics, opioids and non-steroidal anti-inflammatory drugs, to reduce hysteroscopy-associated pain and further studies were recommended. This was a randomized double-blind placebo-controlled trial with balanced randomization (allocation ratio 1:1:1) conducted in a university hospital from May 2014 to November 2014. Two hundred and ten women who had diagnostic outpatient hysteroscopy were randomly divided into three equal groups: Group 1 received oral Tramadol 100 mg, group 2 received Celecoxib 200 mg and group 3 received an oral placebo. All the drugs were given 1 h before the procedure. A patient's perception of pain was assessed during the procedure, immediately afterwards and 30 min after the procedure with the use of a visual analogue scale (VAS). There was a significant difference in the pain scores among the groups during the procedure, immediately afterwards and 30 min after the procedure (P< 0.001, 0.001, <0.001 respectively). Tramadol had significantly lower pain scores when compared with the placebo during the procedure (mean difference = 1.54, 95% confidence interval (CI) (0.86, 2.22), P < 0.001), immediately after the procedure (mean difference = 1.09; 95% CI (0.5, 1.68), P < 0.001) and 30 min later (mean difference = 0.95, 95% CI (0.48, 1.41), P < 0.001). Celecoxib administration also led to significantly lower pain scores than the placebo during the procedure (mean difference = 1.28, 95% CI (0.62, 1.94), P < 0.001), immediately after the procedure (mean

Pharmacokinetics of ibuprofen sodium dihydrate and gastrointestinal tolerability of short-term treatment with a novel, rapidly absorbed formulation.

PubMed

Sörgel, F; Fuhr, U; Minic, M; Siegmund, M; Maares, J; Jetter, A; Kinzig-Schippers, M; Tomalik-Scharte, D; Szymanski, J; Goeser, T; Toex, U; Scheidel, B; Lehmacher, W

2005-03-01

This paper describes four studies investigating the dissolution, plasma pharmacokinetics and safety of a novel, fast-acting ibuprofen formulation, ibuprofen sodium dihydrate. Four separate studies investigated: the in vitro dissolution rates of ibuprofen sodium dihydrate (at pH 1.2, 3.5 and 7.2); the bioavailability of ibuprofen sodium dihydrate (in two pharmacokinetic studies; combined n = 38) compared with conventional ibuprofen, ibuprofen lysinate, ibuprofen arginate and ibuprofen liquagels (all 2 x 200 mg ibuprofen); and the gastroduodenal tolerance of ibuprofen sodium dihydrate and ibuprofen arginate (both 2 x 200 mg ibuprofen t.i.d.) in an endoscopy safety study, where endoscopy was performed at baseline and at the end of each treatment period using a five-point scale to assess the integrity of the gastric and duodenal mucosa. Ibuprofen sodium dihydrate dissolved significantly more rapidly at pH 1.2, 3.5 and 7.2 than conventional ibuprofen, ibuprofen lysinate and ibuprofen liquagels. Ibuprofen sodium dihydrate had similar C(max) to ibuprofen lysinate and ibuprofen liquagels and significantly higher Cmax than conventional ibuprofen (p = 0.002). The mean plasma concentration for ibuprofen sodium dihydrate was significantly higher than for conventional ibuprofen (p = 0.028) 10 minutes post-dose and the t(max) for ibuprofen sodium dihydrate was reached significantly earlier than for conventional ibuprofen (p = 0.018). All three formulations were bioequivalent according to the acceptable boundaries (90% confidence intervals). No statistically significant difference was observed between the ibuprofen formulations in terms of adverse events and specifically with respect to hemorrhagic scores; 41 (46.0%) adverse events (AEs) occurred after administration of ibuprofen sodium dihydrate, and 46 (52.9%) after ibuprofen arginate. One occurrence of an invasive ulcer was observed after administration of ibuprofen arginate. The new formulation of ibuprofen sodium dihydrate

Celecoxib or diclofenac hepatic status in the presence or absence of rebamipide.

PubMed

Murrell, D E; Rahmasari, Y; Denham, J W; Panus, P C; Harirforoosh, S

2015-09-01

Utilization of nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, can produce gastrointestinal ulceration. Thus, cyclooxygenase-2-selective inhibitors, such as celecoxib, and protective agents (e.g. rebamipide) have been employed to alleviate harmful NSAID effects. This study sought to explore the influence of rebamipide on the hepatic outcomes following administration of two commonly prescribed NSAIDs. Rats were given either vehicle or rebamipide (30 mg/kg) orally twice daily for two days, then on the third day respective groups were dosed with either vehicle, celecoxib (40 mg/kg), or diclofenac (10 mg/kg) in addition to a respective dose of vehicle or rebamipide. Livers were collected on day 4 following euthanasia. Hepatic tissue was examined via histopathology and assayed for oxidative stress and specific NSAID concentration. The liver sections were found to be free from structural changes. Oxidative stress biomarkers, reduced glutathione and malondialdehyde, were discovered to be unaltered among the groups tested. The hepatic NSAID concentrations were not significantly affected by the presence of rebamipide. The concomitant administration of rebamipide does not influence the hepatic condition of rats administered either celecoxib or diclofenac at the dosages and over the time course examined.

Differential impairment of aspirin-dependent platelet cyclooxygenase acetylation by nonsteroidal antiinflammatory drugs

PubMed Central

Li, Xuanwen; Fries, Susanne; Li, Ruizhi; Lawson, John A.; Propert, Kathleen J.; Diamond, Scott L.; Blair, Ian A.; FitzGerald, Garret A.; Grosser, Tilo

2014-01-01

The cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs) may be influenced by interactions with antiplatelet doses of aspirin. We sought to quantitate precisely the propensity of commonly consumed NSAIDs—ibuprofen, naproxen, and celecoxib—to cause a drug–drug interaction with aspirin in vivo by measuring the target engagement of aspirin directly by MS. We developed a novel assay of cyclooxygenase-1 (COX-1) acetylation in platelets isolated from volunteers who were administered aspirin and used conventional and microfluidic assays to evaluate platelet function. Although ibuprofen, naproxen, and celecoxib all had the potential to compete with the access of aspirin to the substrate binding channel of COX-1 in vitro, exposure of volunteers to a single therapeutic dose of each NSAID followed by 325 mg aspirin revealed a potent drug–drug interaction between ibuprofen and aspirin and between naproxen and aspirin but not between celecoxib and aspirin. The imprecision of estimates of aspirin consumption and the differential impact on the ability of aspirin to inactivate platelet COX-1 will confound head-to-head comparisons of distinct NSAIDs in ongoing clinical studies designed to measure their cardiovascular risk. PMID:25385584

Effects of celecoxib on cell apoptosis and Fas, FasL and Bcl-2 expression in a BGC-823 human gastric cancer cell line.

PubMed

Li, Qian; Peng, Jie; Liu, Ting; Zhang, Guiying

2017-09-01

Fas, which is an apoptotic-related protein, has an important role in cell apoptosis. Fas ligand (FasL) binds to Fas and activates apoptosis signal transduction. We previously demonstrated that the efficiency of celecoxib inhibited the proliferation and apoptosis of HT-29 colon cancer cell line. The BGC823 cell line was used as an experimental model to evaluate the potential role of celecoxib on gastric cancer cell apoptosis. Inhibitory effects of celecoxib on cell viability were determined by MTT assay. Cell apoptosis was evaluated by flow cytometric analysis and laser confocal microscopy. The results of the present study demonstrated that celecoxib inhibited the viability of BGC823 cells in a concentration- and time-dependent manner. Furthermore, the effect of BGC823 cells apoptosis was increased in a concentration-dependent manner. Western blotting was used to determine the protein expression levels of Fas, FasL, and B-cell lymphoma-2 (Bcl-2). During the celecoxib-induced apoptosis of BGC823 cells, celecoxib upregulated Fas expression and downregulated FasL and Bcl-2 expression in a concentration-dependent manner. These results suggest that celecoxib inhibited the growth and induced apoptosis of BGC823 gastric cancer cells by regulating the protein expression of Fas, FasL and Bcl-2.

Comparative study of the clinical efficacy of the selective cyclooxygenase-2 inhibitor celecoxib compared with loxoprofen in patients with frozen shoulder.

PubMed

Ohta, Satoru; Komai, Osamu; Hanakawa, Hiroyoshi

2014-01-01

This is a randomized comparative study of the efficacy of celecoxib and loxoprofen in patients with frozen shoulder (scapulohumeral periarthritis). Patients with frozen shoulder who presented with pain as the symptom were divided at random into a celecoxib treatment group (100 mg/dose, twice daily; n = 37) and a loxoprofen treatment group (60 mg/dose, 3 times daily; n = 33). Medication was continued for 1-2 weeks in each group. Each patient was asked to rate the pain on a visual analog scale (score 0-5). This score significantly improved (indicating marked alleviation of pain) in both the celecoxib group (from 3.41 ± 0.86 before treatment to 2.30 ± 1.02 after treatment) and the loxoprofen group (from 3.73 ± 0.67 before treatment to 2.76 ± 0.96 after treatment). In the analysis of disappearance of pain, the percentage of patients showing disappearance of nocturnal pain was significantly higher in the celecoxib group (71.4 %) than in the loxoprofen group (36.8 %). The results confirm that celecoxib is comparable to loxoprofen in terms of analgesic efficacy in patients with frozen shoulder. Among other findings, we report that celecoxib was more effective for nocturnal pain than loxoprofen.

An integrated safety analysis of intravenous ibuprofen (Caldolor®) in adults

PubMed Central

Southworth, Stephen R; Woodward, Emily J; Peng, Alex; Rock, Amy D

2015-01-01

Intravenous (IV) nonsteroidal anti-inflammatory drugs such as IV ibuprofen are increasingly used as a component of multimodal pain management in the inpatient and outpatient settings. The safety of IV ibuprofen as assessed in ten sponsored clinical studies is presented in this analysis. Overall, 1,752 adult patients have been included in safety and efficacy trials over 11 years; 1,220 of these patients have received IV ibuprofen and 532 received either placebo or comparator medication. The incidence of adverse events (AEs), serious AEs, and changes in vital signs and clinically significant laboratory parameters have been summarized and compared to patients receiving placebo or active comparator drug. Overall, IV ibuprofen has been well tolerated by hospitalized and outpatient patients when administered both prior to surgery and postoperatively as well as for nonsurgical pain or fever. The overall incidence of AEs is lower in patients receiving IV ibuprofen as compared to those receiving placebo in this integrated analysis. Specific analysis of hematological and renal effects showed no increased risk for patients receiving IV ibuprofen. A subset analysis of elderly patients suggests that no dose adjustment is needed in this higher risk population. This integrated safety analysis demonstrates that IV ibuprofen can be safely administered prior to surgery and continued in the postoperative period as a component of multimodal pain management. PMID:26604816

In vitro permeation characterization of the analgesic ibuprofen and the sunscreen oxybenzone.

PubMed

Gu, Xiaochen; Dannefaer, Jennifer L; Collins, Benjamin R

2008-08-01

Ibuprofen, one of the mostly prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), has been proposed as a topical medication for secondary prevention against skin damage induced by sunburn. The objective of this study was to characterize transmembrane permeation of ibuprofen and sunscreen oxybenzone across poly(dimethyl siloxane) (PDMS) membrane. In vitro diffusion studies were carried out at 37 degrees and 45 degrees C, using a series of ibuprofen and oxybenzone samples, either individually or in combination. Concentrations of ibuprofen and oxybenzone in the receptor compartment for up to 6 h were measured using a high-performance liquid chromatography (HPLC) assay. Ibuprofen and oxybenzone permeated across the PDMS membrane in all diffusion studies. When applied individually, permeation percentages of ibuprofen and oxybenzone ranged from 1.0 to 4.1% and from 13.2 to 25.8%, respectively. When applied in combination, permeation percentages of ibuprofen and oxybenzone were 0.3-1.4% and 7.8-24.3%, respectively. Transmembrane permeation was significantly suppressed when both compounds were present concurrently. High temperature promoted the diffusion process of oxybenzone; a linear correlation was also observed between oxybenzone concentration and its permeation. The proposed permeation enhancement between ibuprofen and oxybenzone was not observed from this study. The potential transdermal interaction and systemic absorption from concurrent application of topical analgesics and sunscreens thus requires further systematic evaluation.

Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans

PubMed Central

Basaran, Kemal Erdem; Villongco, Michael; Ho, Baran; Ellis, Erika; Zarndt, Rachel; Antonova, Julie; Hopkins, Susan R.; Powell, Frank L.

2016-01-01

Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease. PMID:26726885

Ibuprofen Blunts Ventilatory Acclimatization to Sustained Hypoxia in Humans.

PubMed

Basaran, Kemal Erdem; Villongco, Michael; Ho, Baran; Ellis, Erika; Zarndt, Rachel; Antonova, Julie; Hopkins, Susan R; Powell, Frank L

2016-01-01

Ventilatory acclimatization to hypoxia is a time-dependent increase in ventilation and the hypoxic ventilatory response (HVR) that involves neural plasticity in both carotid body chemoreceptors and brainstem respiratory centers. The mechanisms of such plasticity are not completely understood but recent animal studies show it can be blocked by administering ibuprofen, a nonsteroidal anti-inflammatory drug, during chronic hypoxia. We tested the hypothesis that ibuprofen would also block the increase in HVR with chronic hypoxia in humans in 15 healthy men and women using a double-blind, placebo controlled, cross-over trial. The isocapnic HVR was measured with standard methods in subjects treated with ibuprofen (400 mg every 8 hrs) or placebo for 48 hours at sea level and 48 hours at high altitude (3,800 m). Subjects returned to sea level for at least 30 days prior to repeating the protocol with the opposite treatment. Ibuprofen significantly decreased the HVR after acclimatization to high altitude compared to placebo but it did not affect ventilation or arterial O2 saturation breathing ambient air at high altitude. Hence, compensatory responses prevent hypoventilation with decreased isocapnic ventilatory O2-sensitivity from ibuprofen at this altitude. The effect of ibuprofen to decrease the HVR in humans provides the first experimental evidence that a signaling mechanism described for ventilatory acclimatization to hypoxia in animal models also occurs in people. This establishes a foundation for the future experiments to test the potential role of different mechanisms for neural plasticity and ventilatory acclimatization in humans with chronic hypoxemia from lung disease.

Morpho-physiological effects of ibuprofen on Scenedesmus rubescens.

PubMed

Moro, Isabella; Matozzo, Valerio; Piovan, Anna; Moschin, Emanuela; Vecchia, Francesca Dalla

2014-09-01

The pollution of aquatic bodies by drugs is an emerging environmental problem, because of their extensive use in animal and human context. Ibuprofen, 2-[4-(2-methylpropyl)phenyl]propanoic acid, is the non-steroidal anti-inflammatory drug mainly present both in wastewater and in rivers and lakes in Europe. Since in literature there is little information about the effects of ibuprofen on microalgae, in this paper we presented the results on the effects of this molecule at different concentrations (62.5μgL(-1), 250μgL(-1) and 1000μgL(-1)) on cultures of the freshwater microalga Scenedesmus rubescens (P.J.L. Dangeard) E. Kesslet et al. Ibuprofen effects on the alga were assayed at first through analyses of the growth curve. Moreover, analyses of cell morphology, ultrastructure, and photosynthetic pigments were additionally performed. The first negative effect of the drug was on the microalga growth, suggesting a drug action dose-dependent mechanism type, more evident at the concentration of 1000μgL(-1) ibuprofen and in the last phase of the growth curve. In support of this, following ibuprofen exposure, the cells exhibited morphological and ultrastructural alterations, mainly consisting in large cytoplasmic inclusions, probably of lipids and/or carotenoids. The decrease of chlorophyll amounts and, on the contrary, the increase of carotenoids were correlated with a stressful condition induced by drug. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanistic studies of the metabolic chiral inversion of (R)-ibuprofen in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baillie, T.A.; Adams, W.J.; Kaiser, D.G.

1989-05-01

The metabolic chiral inversion of R-(-)-ibuprofen has been studied in human subjects by means of specific deuterium labeling and stereoselective gas chromatography-mass spectrometry methodology. After simultaneous p.o. administration of a mixture of R-(-)-ibuprofen (300 mg) and R-(-)-(3,3,3-2H3)ibuprofen (304 mg) to four adult male volunteers, the enantiomeric composition and deuterium content of the drug in serum, and of the drug and its principal metabolites in urine, were followed over a period of 24 hr. The results of these analyses indicated that: (1) conversion of R-(-)- to S-(+)-ibuprofen takes place with complete retention of deuterium at the beta-methyl (C-3) position; (2) chiralmore » inversion of R-(-)-(2H3)ibuprofen is not subject to a discernible deuterium isotope effect; and (3) replacement of the beta-methyl hydrogen atoms by deuterium has no effect on any of the serum pharmacokinetic parameters for R-(-)- or S-(+)-ibuprofen. These data indicate that the process whereby R-(-)-ibuprofen undergoes metabolic inversion in human subjects does not involve 2,3-dehydroibuprofen as an intermediate, and that the underlying mechanism cannot, therefore, entail a desaturation/reduction sequence.« less

Selective degradation of ibuprofen and clofibric acid in two model river biofilm systems.

PubMed

Winkler, M; Lawrence, J R; Neu, T R

2001-09-01

A field survey indicated that the Elbe and Saale Rivers were contaminated with both clofibric acid and ibuprofen. In Elbe River water we could detect the metabolite hydroxy-ibuprofen. Analyses of the city of Saskatoon sewage effluent discharged to the South Saskatchewan river detected clofibric acid but neither ibuprofen nor any metabolite. Laboratory studies indicated that the pharmaceutical ibuprofen was readily degraded in a river biofilm reactor. Two metabolites were detected and identified as hydroxy- and carboxy-ibuprofen. Both metabolites were observed to degrade in the biofilm reactors. However, in human metabolism the metabolite carboxy-ibuprofen appears and degrades second whereas the opposite occurs in biofilm systems. In biofilms the pharmacologically inactive stereoisomere of ibuprofen is degraded predominantly. In contrast, clofibric acid was not biologically degraded during the experimental period of 21 days. Similar results were obtained using biofilms developed using waters from either the South Saskatchewan or Elbe River. In a sterile reactor no losses of ibuprofen were observed. These results suggested that abiotic losses and adsorption played only a minimal role in the fate of the pharmaceuticals in the river biofilm reactors.

Influence of acidic beverage (Coca-Cola) on pharmacokinetics of ibuprofen in healthy rabbits.

PubMed

Kondal, Amit; Garg, S K

2003-11-01

The study was aimed at determining the effect of Coca-Cola on the pharmacokinetics of ibuprofen in rabbits. In a cross-over study, ibuprofen was given orally in a dose of 56 mg/kg, prepared as 0.5% suspension in carboxymethyl cellulose (CMC) and blood samples (1 ml) were drawn at different time intervals from 0-12 hr. After a washout period of 7 days, Coca-Cola in a dose of (5 ml/kg) was administered along with ibuprofen (56 mg/kg) and blood samples were drawn from 0-12 hr. To these rabbits, 5 ml/kg Coca-Cola was administered once daily for another 7 days. On 8th day, Coca-Cola (5 ml/kg) along with ibuprofen (56 mg/kg), prepared as a suspension was administered and blood samples (1 ml each) were drawn at similar time intervals. Plasma was separated and assayed for ibuprofen by HPLC technique and various pharmacokinetic parameters were calculated. The Cmax and AUC0-alpha of ibuprofen were significantly increased after single and multiple doses of Coca-Cola, thereby indicating increased extent of absorption of ibuprofen. The results warrant the reduction of ibuprofen daily dosage, frequency when administered with Coca-Cola.

Celecoxib, but not indomethacin, ameliorates the hypertensive and perivascular fibrotic actions of cyclosporine in rats: Role of endothelin signaling

DOE Office of Scientific and Technical Information (OSTI.GOV)

El-Mas, Mahmoud M., E-mail: mahelm@hotmail.com; Helmy, Maged W.; Ali, Rabab M.

The immunosuppressant drug cyclosporine (CSA) is used with nonsteroidal antiinflammatory drugs (NSAIDs) in arthritic conditions. In this study, we investigated whether NSAIDs modify the deleterious hypertensive action of CSA and the role of endothelin (ET) receptors in this interaction. Pharmacologic, protein expression, and histopathologic studies were performed in rats to investigate the roles of endothelin receptors (ET{sub A}/ET{sub B}) in the hemodynamic interaction between CSA and two NSAIDs, indomethacin and celecoxib. Tail-cuff plethysmography measurements showed that CSA (20 mg kg{sup −1} day{sup −1}, 10 days) increased systolic blood pressure (SBP) and heart rate (HR). CSA hypertension was associated with renalmore » perivascular fibrosis and divergent changes in immunohistochemical signals of renal arteriolar ET{sub A} (increases) and ET{sub B} (decreases) receptors. While these effects of CSA were preserved in rats treated concomitantly with indomethacin (5 mg kg{sup −1} day{sup −1}), celecoxib (10 mg kg{sup −1} day{sup −1}) abolished the pressor, tachycardic, and fibrotic effects of CSA and normalized the altered renal ET{sub A}/ET{sub B} receptor expressions. Selective blockade of ET{sub A} receptors by atrasentan (5 mg kg{sup −1} day{sup −1}) abolished the pressor response elicited by CSA or CSA plus indomethacin. Alternatively, BQ788 (ET{sub B} receptor blocker, 0.1 mg kg{sup −1} day{sup −1}) caused celecoxib-sensitive elevations in SBP and potentiated the pressor response evoked by CSA. Together, the improved renovascular fibrotic and endothelin receptor profile (ET{sub A} downregulation and ET{sub B} upregulation) mediate, at least partly, the protective effect of celecoxib against the hypertensive effect of CSA. Clinically, the use of celecoxib along with CSA in the management of arthritic conditions might provide hypertension-free regimen. - Highlights: • Chronic CSA causes hypertension and renal perivascular fibrosis in

Enhanced inhibition of urinary bladder cancer growth and muscle invasion by allyl isothiocyanate and celecoxib in combination

PubMed Central

Zhang, Yuesheng

2013-01-01

Allyl isothiocyanate (AITC) occurs in cruciferous vegetables that are commonly consumed by humans and has been shown to inhibit urinary bladder cancer growth and progression in previous preclinical studies. However, AITC does not significantly modulate cyclooxygenase-2 (Cox-2), whose oncogenic activity has been well documented in bladder cancer and other cancers. Celecoxib is a selective Cox-2 inhibitor and has been widely used for treatment of several diseases. Celecoxib has also been evaluated in bladder cancer patients, but its efficacy against bladder cancer as a single agent remains unclear. In a syngeneic rat model of orthotopic bladder cancer, treatment of the animals with the combination of AITC and celecoxib at low dose levels (AITC at 1mg/kg and celecoxib at 10mg/kg) led to increased or perhaps synergistic inhibition of bladder cancer growth and muscle invasion, compared with each agent used alone. The combination regime was also more effective than each single agent in inhibiting microvessel formation and stimulating microvessel maturation in the tumor tissues. The anticancer efficacy of the combination regime was associated with depletion of prostaglandin E2, a key downstream signaling molecule of Cox-2, caspase activation and downregulation of vascular endothelial growth factor in the tumor tissues. These data show that AITC and celecoxib complement each other for inhibition of bladder cancer and provide a novel combination approach for potential use for prevention or treatment of human bladder cancer. PMID:23946495

Association of Celecoxib Use With Decreased Opioid Requirements After Head and Neck Cancer Surgery With Free Tissue Reconstruction.

PubMed

Carpenter, Patrick S; Shepherd, Hailey M; McCrary, Hilary; Torrecillas, Vanessa; Kull, Amanda; Hunt, Jason P; Monroe, Marcus M; Buchmann, Luke O; Cannon, Richard B

2018-04-18

Head and neck cancer (HNC) surgery with free tissue reconstruction is associated with considerable postoperative pain. Opioids are typically used but can have adverse effects, including respiratory depression and high rates of dependence and addiction. Safe alternative analgesics that minimize opioid requirements are beneficial in HNC surgery. To investigate the association of celecoxib use with opioid requirements in the postoperative setting after HNC surgery with free tissue reconstruction. A retrospective, matched-cohort study of 147 patients who had undergone HNC surgery with free tissue reconstruction between June 2015 and Sept 2017 in an academic cancer hospital. Patients were separated into groups based on whether celecoxib had been used perioperatively or not. These groups were then matched by stage and site resulting in 102 included participants (51 celecoxib, 51 control). Oral, intravenous (IV), and total morphine equivalents used in the postoperative setting per patient per day. There were 51 patients in the celecoxib cohort (19 women and 32 men) and 51 patients in the control cohort (20 women and 31 men) who met inclusion criteria after clinicopathologic data were matched. The mean age of the celecoxib and control cohorts was 61.6 years and 66.1 years, respectively. Treatment with celecoxib in the postoperative setting was associated with decreased mean use of opioids in oral (mean difference, 9.9 mg/d; 95% CI, -1.2 to 21.1), IV (mean difference, 3.9 mg/d; 95% CI, 1.0-6.8), and total (mean difference, 14 mg/d; 95% CI, 2.6-25.4) amount of morphine equivalents per day. When patients were matched to surgical procedure, the effect was more significant. Patients who underwent composite oral resection and received celecoxib had decreased opioid use in oral (mean difference, 25 mg/d; 95% CI, 12.5-25.4), IV (mean difference, 3.4 mg/d; 95% CI, 1.5-5.5), and total (mean difference, 28.4 mg/d; 95% CI, 15.7-41.5) amounts compared with those in the control group

Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells.

PubMed

Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

2005-01-01

Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and

Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

PubMed Central

Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

2005-01-01

Introduction Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. Methods MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. Results The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with

Ibuprofen Ameliorates Fatigue- and Depressive-like Behavior in Tumor-bearing Mice

PubMed Central

Norden, Diana M.; McCarthy, Donna O.; Bicer, Sabahattin; Devine, Raymond; Reiser, Peter J.; Godbout, Jonathan P.; Wold, Loren E.

2015-01-01

Aims Cancer-related fatigue (CRF) is often accompanied by depressed mood, both of which reduce functional status and quality of life. Research suggests that increased expression of pro-inflammatory cytokines are associated with skeletal muscle wasting and depressive- and fatigue- like behaviors in rodents and cancer patients. We have previously shown that treatment with ibuprofen, a nonsteroidal anti-inflammatory drug, preserved muscle mass in tumor-bearing mice. Therefore, the purpose of the present study was to determine the behavioral effects of ibuprofen in a mouse model of CRF. Main Methods Mice were injected with colon-26 adenocarcinoma cells and treated with ibuprofen (10mg/kg) in the drinking water. Depressive-like behavior was determined using the forced swim test (FST). Fatigue-like behaviors were determined using voluntary wheel running activity (VWRA) and grip strength. The hippocampus, gastrocnemius muscle, and serum were collected for cytokine analysis. Key Findings Tumor-bearing mice showed depressive-like behavior in the FST, which was not observed in mice treated with ibuprofen. VWRA and grip strength declined in tumor-bearing mice, and ibuprofen attenuated this decline. Tumor-bearing mice had decreased gastrocnemius muscle mass and increased expression of IL-6, MAFBx and MuRF mRNA, biomarkers of protein degradation, in the muscle. Expression of IL-1β and IL-6 was also increased in the hippocampus. Treatment with ibuprofen improved muscle mass and reduced cytokine expression in both the muscle and hippocampus of tumor-bearing mice. Significance Ibuprofen treatment reduced skeletal muscle wasting, inflammation in the brain, and fatigue- and depressive-like behavior in tumor-bearing mice. Therefore, ibuprofen warrants evaluation as an adjuvant treatment for CRF. PMID:26498217

Using cyclodextrin complexation to enhance secondary photoprotection of topically applied ibuprofen.

PubMed

Godwin, Donald A; Wiley, Cody J; Felton, Linda A

2006-01-01

Each year millions of people are overexposed to the sun resulting in photodamage of the skin. Secondary photoprotection is the application of medicinal agents to the body after sun exposure to reduce this damage. The objective of this study was to determine the affects of hydroxypropyl-beta-cyclodextrin (HPCD) complexation on the secondary photoprotective properties of topically applied ibuprofen. Complexation of ibuprofen by HPCD was demonstrated by differential scanning calorimetry, while solubilities were determined using HPLC. A linear (r2>0.999) relationship was found between ibuprofen solubility and HPCD concentration. For subsequent experiments, the concentration of ibuprofen was held constant at the solubility in 10% HPCD (10.6 mg/ml), while the HPCD concentration varied from 0 to 20% (w/w). In vitro transdermal permeation experiments demonstrated a parabolic relationship between transdermal kinetic parameters and HPCD concentration, with maximum values for both flux and skin accumulation occurring with the 10% HPCD formulation. In vivo experiments were performed by exposing hairless mice to UV radiation and applying ibuprofen-HPCD formulations topically at various times following UV exposure. Edema and epidermal lipid damage data demonstrated that application of ibuprofen-HPCD formulations within 1h of UV exposure provided significant photoprotection.

Cutaneous irritancy of an ibuprofen medicated plaster in healthy volunteers.

PubMed

Maganji, Manisha; Connolly, Mark P; Bhatt, Aomesh

2018-04-01

To assess the irritation and contact sensitization potential of a 200 mg ibuprofen medicated plaster. This double-blind, phase-1 placebo controlled study had two phases; the induction phase to evaluate the irritant potential of continuous application of the plaster, and the challenge phase to assess contact sensitivity (allergy). The cumulative irritancy potential was evaluated using an adaptation of the Shelanski method. Healthy adults (≥18 years of age) (N = 210) were treated simultaneously with one ibuprofen medicated and one placebo plaster applied in a randomized fashion to either the left or right side of the lower back. During the induction phase, plasters were applied on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 and the final plaster removed on Day 22. At each scheduled visit plasters and applications sites were assessed for degree of adhesion and skin irritation (score of 1 = no irritation to 7 = strong reaction spreading beyond test sites), respectively. The challenge phase followed a two-week washout period. A plaster was applied on Day 36 for 48 h and assessment occurred on Days 38, 39, and 40. The mean cumulative irritation score during the induction phase was lower for the ibuprofen medicated plaster than the placebo plaster (0.32 vs. 1.23, respectively). Three (1.4%) subjects experience a dermal reaction of grade ≥3 for the ibuprofen medicated plaster compared with 27 (12.7%) for the placebo plaster. Following challenge with ibuprofen or placebo plasters, 12 subjects (6.2%) with the ibuprofen medicated plaster and four (2.2%) with the placebo plaster had skin reaction of assessment grade higher than the induction phase. One subject for the ibuprofen and two for the placebo plaster had reactions with grade >2. No subjects showed an increase in sensitization on Day 39 or 40 compared with Day 38. The findings indicate that the both the irritancy and contact sensitization of the ibuprofen medicated plaster is acceptable.

A Multi-Center, Randomized, Double-Blind Placebo-Controlled Trial of Intravenous-Ibuprofen (IV-Ibuprofen) for Treatment of Pain in Post-Operative Orthopedic Adult Patients

PubMed Central

Singla, Neil; Rock, Amy; Pavliv, Leo

2010-01-01

Objective To determine whether pre- and post-operative administration of intravenous ibuprofen (IV-ibuprofen) can significantly decrease pain and morphine use when compared with placebo in adult orthopedic surgical patients. Design This was a multi-center, randomized, double-blind placebo-controlled trial. Setting This study was completed at eight hospitals; six in the United States and two in South Africa. Patients A total of 185 adult patients undergoing elective orthopedic surgery. Interventions Patients were randomized to receive either 800 mg IV-ibuprofen or placebo every 6 hours, with the first dose administered pre-operatively. Additionally, all patients had access to intravenous morphine for rescue. Outcome Measures Efficacy of IV-ibuprofen was demonstrated by measuring the patient's self assessment of pain using a visual analog scale (VAS; assessed with movement and at rest) and a verbal response scale (VRS). Morphine consumption during the post-operative period was also assessed. Results In the immediate post-operative period, there was a 25.8% reduction in mean area under the curve-VAS assessed with movement (AUC-VASM) in patients receiving IV-ibuprofen (P < 0.001); a 31.8% reduction in mean AUC-VAS assessed at rest (AUC-VASR; P < 0.001) and a 20.2% reduction in mean VRS (P < 0.001) compared to those receiving placebo. Patients receiving IV-ibuprofen used 30.9% less morphine (P < 0.001) compared to those receiving placebo. Similar treatment emergent adverse events occurred in both study groups and there were no significant differences in the incidence of serious adverse events. Conclusion Pre- and post-operative administration of IV-ibuprofen significantly reduced both pain and morphine use in orthopedic surgery patients in this prospective randomized placebo-controlled trial. PMID:20609131

Ibuprofen reverts antifungal resistance on Candida albicans showing overexpression of CDR genes.

PubMed

Ricardo, Elisabete; Costa-de-Oliveira, Sofia; Dias, Ana Silva; Guerra, José; Rodrigues, Acácio Gonçalves; Pina-Vaz, Cidália

2009-06-01

Several mechanisms may be associated with Candida albicans resistance to azoles. Ibuprofen was described as being able to revert resistance related to efflux activity in Candida. The aim of this study was to uncover the molecular base of antifungal resistance in C. albicans clinical strains that could be reverted by ibuprofen. Sixty-two clinical isolates and five control strains of C. albicans were studied: the azole susceptibility phenotype was determined according to the Clinical Laboratory for Standards Institute, M27-A2 protocol and minimal inhibitory concentration values were recalculated with ibuprofen (100 microg mL(-1)); synergistic studies between fluconazole and FK506, a Cdr1p inhibitor, were performed using an agar disk diffusion assay and were compared with ibuprofen results. Gene expression was quantified by real-time PCR, with and without ibuprofen, regarding CDR1, CDR2, MDR1, encoding for efflux pumps, and ERG11, encoding for azole target protein. A correlation between susceptibility phenotype and resistance gene expression profiles was determined. Ibuprofen and FK506 showed a clear synergistic effect when combined with fluconazole. Resistant isolates reverting to susceptible after incubation with ibuprofen showed CDR1 and CDR2 overexpression especially of the latter. Conversely, strains that did not revert displayed a remarkable increase in ERG11 expression along with CDR genes. Ibuprofen did not alter resistance gene expression significantly (P>0.05), probably acting as a Cdrp blocker.

Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME

PubMed Central

Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag

2017-01-01

AIM To counteract/reveal celecoxib-induced toxicity and NO system involvement. METHODS Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. RESULTS This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). CONCLUSION BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs’ post-surgery application and NO system involvement. PMID:28839430

Celecoxib-induced gastrointestinal, liver and brain lesions in rats, counteraction by BPC 157 or L-arginine, aggravation by L-NAME.

PubMed

Drmic, Domagoj; Kolenc, Danijela; Ilic, Spomenko; Bauk, Lara; Sever, Marko; Zenko Sever, Anita; Luetic, Kresimir; Suran, Jelena; Seiwerth, Sven; Sikiric, Predrag

2017-08-07

To counteract/reveal celecoxib-induced toxicity and NO system involvement. Celecoxib (1 g/kg b.w. ip) was combined with therapy with stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade [N(G)-nitro-L-arginine methyl ester (L-NAME)] (5 mg/kg ip) given alone and/or combined immediately after celecoxib. Gastrointestinal, liver, and brain lesions and liver enzyme serum values in rats were assessed at 24 h and 48 h thereafter. This high-dose celecoxib administration, as a result of NO system dysfunction, led to gastric, liver, and brain lesions and increased liver enzyme serum values. The L-NAME-induced aggravation of the lesions was notable for gastric lesions, while in liver and brain lesions the beneficial effect of L-arginine was blunted. L-arginine counteracted gastric, liver and brain lesions. These findings support the NO system mechanism(s), both NO system agonization (L-arginine) and NO system antagonization (L-NAME), that on the whole are behind all of these COX phenomena. An even more complete antagonization was identified with BPC 157 (at both 24 h and 48 h). A beneficial effect was evident on all the increasingly negative effects of celecoxib and L-NAME application and in all the BPC 157 groups (L-arginine + BPC 157; L-NAME + BPC 157; L-NAME + L-arginine + BPC 157). Thus, these findings demonstrated that BPC 157 may equally counteract both COX-2 inhibition (counteracting the noxious effects of celecoxib on all lesions) and additional NOS blockade (equally counteracting the noxious effects of celecoxib + L-NAME). BPC 157 and L-arginine alleviate gastrointestinal, liver and brain lesions, redressing NSAIDs' post-surgery application and NO system involvement.

Effects of humidity and surfaces on the melt crystallization of ibuprofen.

PubMed

Lee, Dong-Joo; Lee, Suyang; Kim, Il Won

2012-01-01

Melt crystallization of ibuprofen was studied to understand the effects of humidity and surfaces. The molecular self-assembly during the amorphous-to-crystal transformation was examined in terms of the nucleation and growth of the crystals. The crystallization was on Al, Au, and self-assembled monolayers with -CH(3), -OH, and -COOH functional groups. Effects of the humidity were studied at room temperature (18-20 °C) with relative humidity 33%, 75%, and 100%. Effects of the surfaces were observed at -20 °C (relative humidity 36%) to enable close monitoring with slower crystal growth. The nucleation time of ibuprofen was faster at high humidity conditions probably due to the local formation of the unfavorable ibuprofen melt/water interface. The crystal morphologies of ibuprofen were governed by the nature of the surfaces, and they could be associated with the growth kinetics by the Avrami equation. The current study demonstrated the effective control of the melt crystallization of ibuprofen through the melt/atmosphere and melt/surface interfaces.

Ibuprofen Differentially Affects Supraspinatus Muscle and Tendon Adaptations to Exercise in a Rat Model

PubMed Central

Rooney, Sarah Ilkhanipour; Baskin, Rachel; Torino, Daniel J.; Vafa, Rameen P.; Khandekar, Pooja S.; Kuntz, Andrew F.; Soslowsky, Louis J.

2017-01-01

Background Previous studies have shown that ibuprofen is detrimental to tissue healing following acute injury; however, the effects of ibuprofen when combined with non-injurious exercise are debated. Hypothesis We hypothesized that administration of ibuprofen to rats undergoing a non-injurious treadmill exercise protocol would abolish the beneficial adaptations found with exercise but have no effect on sedentary muscle and tendon properties. Study Design Controlled laboratory study Methods Rats were divided into exercise or cage activity (sedentary) groups and acute (a single bout of exercise followed by 24 hours of rest) and chronic (2 or 8 weeks of repeated exercise) time points. Half of the rats received ibuprofen to investigate the effects of this drug over time when combined with different activity levels (exercise and sedentary). Supraspinatus tendons were used for mechanical testing and histology (organization, cell shape, cellularity), and supraspinatus muscles were used for morphological (fiber CSA, centrally nucleated fibers) and fiber type analysis. Results Chronic intake of ibuprofen did not impair supraspinatus tendon organization or mechanical adaptations (stiffness, modulus, max load, max stress, dynamic modulus, or viscoelastic properties) to exercise. Tendon mechanical properties were not diminished and in some instances increased with ibuprofen. In contrast, total supraspinatus muscle fiber cross-sectional area decreased with ibuprofen at chronic time points, and some fiber type-specific changes were detected. Conclusions Chronic administration of ibuprofen does not impair supraspinatus tendon mechanical properties in a rat model of exercise but does decrease supraspinatus muscle fiber cross-sectional area. Clinically, these findings suggest that ibuprofen does not detrimentally affect regulation of supraspinatus tendon adaptions to exercise but does decrease muscle growth. Individuals should be advised on the risk of decreased muscle hypertrophy

Treatment options for rheumatoid arthritis: celecoxib, leflunomide, etanercept, and infliximab.

PubMed

Luong, B T; Chong, B S; Lowder, D M

2000-06-01

To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA). A MEDLINE search (1966-January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data. All controlled and uncontrolled trials were reviewed. Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost. Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy. Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.

LY3127760, a Selective Prostaglandin E4 (EP4) Receptor Antagonist, and Celecoxib: A Comparison of Pharmacological Profiles

PubMed Central

Smith, Claire; Hu, Leijun; Coutant, David E.; Whitehurst, Kelly; Phipps, Krista; McNearney, Terry Ann; Yang, Xiao; Ackermann, Bradley; Pottanat, Thomas; Landschulz, William

2017-01-01

Abstract Safety, tolerability, and pharmacology profiles of LY3127760, an EP4 antagonist, were explored in healthy subjects in a subject/investigator‐blind, parallel‐group, multiple‐ascending dose study. Cohorts consisted of 13 patients randomized to LY3127760, celecoxib (400 mg), or placebo (9:2:2 ratio) for 28 days. LY3127760 was well tolerated; the most commonly observed adverse events were gastrointestinal, similar to celecoxib. LY3127760 increased release of ex vivo tumor necrosis factor alpha after lipopolysaccharide/prostaglandin E2 stimulation when compared with placebo, suggesting a dose‐dependent blockade of the EP4 receptor. Compared with placebo, 24‐h urinary excretion of prostaglandin E metabolite was modestly increased; prostacyclin metabolite was inhibited; and thromboxane A2 metabolite was unchanged. Effects on sodium and potassium excretion were similar to those of celecoxib. We conclude that LY3127760 demonstrated similar effects on prostacyclin synthesis and renal sodium retention as celecoxib. These data support exploration of LY3127760 at daily doses of 60 mg to 600 mg in phase II trials. This trial's registration number: NCT01968070. PMID:28857461

Controlled release of ibuprofen by meso–macroporous silica

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santamaría, E., E-mail: esthersantamaria@ub.edu; Maestro, A.; Porras, M.

2014-02-15

Structured meso–macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (EO{sub 19}PO{sub 39}EO{sub 19}) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption–desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso–macroporous materials. The effect of the materials’ properties on IBU drug loading and releasemore » was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system. - Graphical abstract: Ibuprofen release profiles for the materials obtained from samples P84{sub m}eso (black diamonds), P84{sub 2}0% (white squares), P84

Effects of pH, dissolved organic matter, and salinity on ibuprofen sorption on sediment.

PubMed

Oh, Sanghwa; Shin, Won Sik; Kim, Hong Tae

2016-11-01

Ibuprofen is well known as one of the most frequently detected pharmaceuticals and personal care products (PPCPs) in rivers. However, sorption of ibuprofen onto sediment has not been considered in spite of its high K ow (3.5). In this study, the effects of various environmental conditions such as pH (4, 5.3, and 7), the concentrations of dissolved organic matters (0 to 1.0 mM citrate and urea), salinity (0, 10, 20, and 30 part per thousand), and presence of other PPCP (salicylic acid) on ibuprofen sorption were investigated. Linear model mainly fitted the experimental data for analysis. The distribution coefficient (K d ) in the linear model decreased from 6.76 at pH 4 to near zero at pH 7, indicating that neutral form of ibuprofen at pH below pKa (5.2) was easily sorbed onto the sediment whereas the sorption of anionic form at pH over pKa was not favorable. To investigate the effect of dissolved organic matters (DOMs) on ibuprofen sorption, citrate and urea were used as DOMs. As citrate concentration increased, the K d value decreased but urea did not interrupt the ibuprofen sorption. Citrate has three carboxyl functional groups which can attach easily ibuprofen and hinder its sorption onto sediment. Salinity also affected ibuprofen sorption due to decrease of the solubility of ibuprofen as salinity increased. In competitive sorption experiment, the addition of salicylic acid also led to enhance ibuprofen sorption. Conclusively, ibuprofen can be more easily sorbed onto the acidified sediments of river downstream, especially estuaries or near-shore environment with low DOM concentration.

Effect of racemic ibuprofen dose on the magnitude and duration of platelet cyclo-oxygenase inhibition: relationship between inhibition of thromboxane production and the plasma unbound concentration of S(+)-ibuprofen.

PubMed

Evans, A M; Nation, R L; Sansom, L N; Bochner, F; Somogyi, A A

1991-02-01

1. Four healthy male subjects received racemic ibuprofen (200, 400, 800 and 1200 mg), orally, on four occasions, 2 weeks apart, according to a four-way Latin-square design, in order to investigate the influence of increasing dose of ibuprofen on the magnitude and duration of its antiplatelet effect as well as on the relationship between such effect and drug concentration. 2. The antiplatelet effect of ibuprofen was assessed by measuring the inhibition of platelet thromboxane B2 (TXB2) generation during the controlled clotting of whole blood. The plasma unbound concentration of S(+)-ibuprofen, the enantiomer shown in an in vitro study to be responsible for the inhibitory effect of platelet TXB2 generation, was measured using an enantioselective method. 3. The maximum percentage inhibition of TXB2 generation increased significantly with dose from a mean +/- s.d. of 93.4 +/- 1.2% after the 200 mg dose to 98.8 +/- 0.3% after the 1200 mg dose, and there was an increase with dose in the duration of inhibition of TXB2 generation. The effect of ibuprofen on platelet TXB2 generation was transient and mirrored the time-course of unbound S(+)-ibuprofen in plasma; on all but one of the 16 occasions, serum TXB2 concentrations returned to at least within 10% of the pretreatment concentrations within 24 h of ibuprofen administration. 4. For each subject, the relationship between the percentage inhibition of TXB2 generation and the unbound concentration of S(+)-ibuprofen in plasma was modelled according to a sigmoidal Emax equation. The mean plasma unbound concentration of S(+)-ibuprofen required to inhibit platelet TXB2 generation by 50% (EC50) was 9.8 +/- 1.0 micrograms l-1.(ABSTRACT TRUNCATED AT 250 WORDS)

β-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

NASA Astrophysics Data System (ADS)

Baradari, Hiba; Damia, Chantal; Dutreih-Colas, Maggy; Champion, Eric; Chulia, Dominique; Viana, Marylène

2011-10-01

Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous β-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous β-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and β-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on β-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

Stability and Ocular Pharmacokinetics of Celecoxib-Loaded Nanoparticles Topical Ophthalmic Formulations.

PubMed

Ibrahim, Mohammed Mostafa; Abd-Elgawad, Abd-Elgawad Helmy; Soliman, Osama Abd-Elazeem; Jablonski, Monica M

2016-12-01

A spontaneous emulsification and/or solvent diffusion method was used for the preparation of celecoxib-loaded nanoparticles (NPs) using polymers, including chitosan (CS), sodium alginate, poly-ε-caprolactone (PCL), poly-l-lactide, and poly-d,l-lactide-co-glycolide. NPs were incorporated into vehicles (eye drops, in situ gelling system, and gel). Formulations were subjected to an accelerated stability study by storing them at elevated temperatures of 30, 35, and 45°C for 6 months. Formulations were evaluated monthly for general appearance, pH, viscosity, particle size, polydispersity index, zeta potential, and drug content. Gels containing CS-NPs and PCL-NPs were selected for an ocular pharmacokinetics study using Sprague-Dawley rats due to their high stability and long shelf lives (24.56 and 33.76 months, respectively). The gel improved NP stability by keeping it inside its network structure, which protected them from aggregation and interacting with water. Our formulations improved celecoxib bioavailability due to their bioadhesivness, thus preventing their rapid removal. Also, NPs acted as drug reservoirs that adhered to eye surface and continuously released the drug. The availability of celecoxib in all eye tissues and its absence in plasma suggests that our formulation could be used for anterior eye disorders and also for treatment of diseases associated with the posterior eye with no systemic side effects. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Does ibuprofen treatment in patent ductus arteriosus alter oxygen free radicals in premature infants?

PubMed

Akar, Melek; Yildirim, Tulin G; Sandal, Gonca; Bozdag, Senol; Erdeve, Omer; Altug, Nahide; Uras, Nurdan; Oguz, Serife S; Dilmen, Ugur

2017-04-01

Introduction Ibuprofen is used widely to close patent ductus arteriosus in preterm infants. The anti-inflammatory activity of ibuprofen may also be partly due to its ability to scavenge reactive oxygen species and reactive nitrogen species. We evaluated the interaction between oxidative status and the medical treatment of patent ductus arteriosus with two forms of ibuprofen. Materials and methods This study enrolled newborns of gestational age ⩽32 weeks, birth weight ⩽1500 g, and postnatal age 48-96 hours, who received either intravenous or oral ibuprofen to treat patent ductus arteriosus. Venous blood was sampled before ibuprofen treatment from each patient to determine antioxidant and oxidant concentrations. Secondary samples were collected 24 hours after the end of the treatment. Total oxidant status and total antioxidant capacity were measured using Erel's method. This prospective randomised study enrolled 102 preterm infants with patent ductus arteriosus. The patent ductus arteriosus closure rate was significantly higher in the oral ibuprofen group (84.6 versus 62%) after the first course of treatment (p=0.011). No significant difference was found between the pre- and post-treatment total oxidant status and total antioxidant capacity in the groups. Discussion Ibuprofen treatment does not change the total oxidant status or total antioxidant capacity. We believe that the effect of ibuprofen treatment in inducing ischaemia overcomes the scavenging effect of ibuprofen.

Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with celecoxib for patients with locally advanced esophageal cancer.

PubMed

Cleary, James M; Mamon, Harvey J; Szymonifka, Jackie; Bueno, Raphael; Choi, Noah; Donahue, Dean M; Fidias, Panos M; Gaissert, Henning A; Jaklitsch, Michael T; Kulke, Matthew H; Lynch, Thomas P; Mentzer, Steven J; Meyerhardt, Jeffrey A; Swanson, Richard S; Wain, John; Fuchs, Charles S; Enzinger, Peter C

2016-07-13

Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation. This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery. Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases. The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted. Clinicaltrials.gov: NCT00137852 , registered August 29, 2005.

Comparison of gastroduodenal ulcer incidence in healthy Japanese subjects taking celecoxib or loxoprofen evaluated by endoscopy: a placebo-controlled, double-blind 2-week study.

PubMed

Sakamoto, C; Kawai, T; Nakamura, S; Sugioka, T; Tabira, J

2013-02-01

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are widely prescribed globally, their chronic use increases the risk of upper gastrointestinal (GI) damage. Cyclooxygenase-2-selective NSAIDs are considered to reduce this risk. Current guidelines in Japan recommend loxoprofen sodium (loxoprofen), a pro-drug in the propionic acid class of nonselective NSAIDs, as first-line therapy in rheumatoid arthritis. To confirm the superiority of celecoxib, a cyclooxygenase-2-selective NSAID, to loxoprofen in the incidence of gastroduodenal (GD) endoscopic ulcers. A randomised, multicentre, placebo-controlled, double-blind, phase IV clinical trial in healthy Japanese volunteers [mean age 57.5 (range: 40-74) years; >70% female], stratified by Helicobacter pylori status at screening (~40% positive) and randomised 2:2:1 to receive celecoxib 100 mg b.d., loxoprofen 60 mg t.d.s. or placebo. Primary end point was incidence of any GD endoscopic ulcers after 2 weeks of treatment. Of 190 randomised subjects, 189 received at least one dose of celecoxib (n = 76), loxoprofen (n = 76), or placebo (n = 37). Incidence of GD ulcers was 1.4%, 27.6% and 2.7% in the celecoxib, loxoprofen and placebo groups respectively (P < 0.0001 in favour of the celecoxib group); incidence of adverse events (AEs) was 34.2%, 51.3% and 21.6% in the celecoxib, loxoprofen and placebo groups respectively. No serious or severe AEs were reported. Celecoxib 100 mg b.d. was superior to loxoprofen 60 mg t.d.s. regarding the incidence of gastro-duodenal endoscopic ulcers over 2 weeks. Celecoxib was well tolerated and no major safety concerns were observed. © 2012 Blackwell Publishing Ltd.

Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs.

PubMed

Ogundeji, Adepemi O; Pohl, Carolina H; Sebolai, Olihile M

2016-08-01

The usage of fluconazole and amphotericin B in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. Thus, there is a constant need to find new drugs to better manage fungal infections. Toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells. In vitro susceptibility tests, including a checkerboard assay, were performed to assess the response of Cryptococcus neoformans and Cryptococcus gattii to the above-mentioned anti-inflammatory drugs. Next, the capacity of these two drugs to induce stress as well as their mode of action in the killing of cryptococcal cells was determined. The studied fungal strains revealed a response to both aspirin and ibuprofen that was dose dependent, with ibuprofen exerting greater antimicrobial action. More importantly, the MICs of these drugs did not negatively (i) affect growth or (ii) impair the functioning of macrophages; rather, they enhanced the ability of these immune cells to phagocytose cryptococcal cells. Ibuprofen was also shown to act in synergy with fluconazole and amphotericin B. The treatment of cryptococcal cells with aspirin or ibuprofen led to stress induction via activation of the high-osmolarity glycerol (HOG) pathway, and cell death was eventually achieved through reactive oxygen species (ROS)-mediated membrane damage. The presented data highlight the potential clinical application of aspirin and ibuprofen as candidate anti-Cryptococcus drugs. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Effects of Humidity and Surfaces on the Melt Crystallization of Ibuprofen

PubMed Central

Lee, Dong-Joo; Lee, Suyang; Kim, Il Won

2012-01-01

Melt crystallization of ibuprofen was studied to understand the effects of humidity and surfaces. The molecular self-assembly during the amorphous-to-crystal transformation was examined in terms of the nucleation and growth of the crystals. The crystallization was on Al, Au, and self-assembled monolayers with –CH3, –OH, and –COOH functional groups. Effects of the humidity were studied at room temperature (18–20 °C) with relative humidity 33%, 75%, and 100%. Effects of the surfaces were observed at −20 °C (relative humidity 36%) to enable close monitoring with slower crystal growth. The nucleation time of ibuprofen was faster at high humidity conditions probably due to the local formation of the unfavorable ibuprofen melt/water interface. The crystal morphologies of ibuprofen were governed by the nature of the surfaces, and they could be associated with the growth kinetics by the Avrami equation. The current study demonstrated the effective control of the melt crystallization of ibuprofen through the melt/atmosphere and melt/surface interfaces. PMID:22949861

Penetration and pharmacokinetics of non-steroidal anti-inflammatory drugs in rat prostate tissue.

PubMed

Yellepeddi, Venkata K; Radhakrishnan, Jayashree; Radhakrishnan, Rajan

2018-02-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) involves inflammation of the prostate and affects the quality of life of men of all ages. It is well reported in clinical studies that the treatment for CP/CPPS using nonsteroidal anti-inflammatory drugs (NSAIDs) produced favorable outcomes. However, currently, there are no guidelines on choice of the NSAIDs for the treatment of CP/CPPS. Therefore, in the current research study, we evaluated the prostate tissue penetration of four NSAIDs in rats to provide guidance on choice of NSAIDs for the treatment of CP/CPPS. Male Sprague-Dawley rats were administered orally with four NSAIDs viz. celecoxib, diclofenac, ibuprofen, and naproxen at 500 mg/kg dose. The animals were then sacrificed at various time points, and their prostate tissues were harvested. The NSAIDs were then extracted from the prostate tissues using liquid extraction technique, and their concentration in prostate tissue was quantified using high-performance liquid chromatography (HPLC). The prostate tissue penetration and related pharmacokinetic parameters were evaluated by non-compartmental analysis. The HPLC method for quantifying NSAIDs in prostate tissue resulted in single, sharp peaks without any interference and all validation parameters were within limits. Celecoxib showed the highest area under the curve (AUC) [146.50 ± 2.75 μg/mL*h] of all NSAID's. A two-factor analysis of variance (ANOVA) with replication indicated an overall statistically significant difference in the pharmacokinetic parameters for celecoxib, diclofenac, ibuprofen, and naproxen. This study for the first time reported the relative prostate tissue penetration of four NSAIDs. The pharmacokinetic data indicated that celecoxib has the highest penetration and retention in rat prostate tissues. Therefore, celecoxib may be considered as a better choice for the treatment CP/CPPS involving NSAIDs. © 2017 Wiley Periodicals, Inc.

In-vitro and in-vivo inhibition of melanoma growth and metastasis by the drug combination of celecoxib and dacarbazine.

PubMed

Sadhu, Satya S; Wang, Shenggang; Averineni, Ranjith K; Seefeldt, Teresa; Yang, Yang; Guan, Xiangming

2016-12-01

Celecoxib has been found to be effective in cancer prevention and treatment. Its combination with other chemotherapeutic agents was reported to produce synergistic/additive effects on various cancers. Dacarbazine (DTIC) is one of the most commonly used drugs in the treatment of metastatic melanoma. This investigation aimed to determine the in-vitro and in-vivo effects of the drug combination of celecoxib and DTIC on melanoma growth and metastasis. Melanoma cells B16-F10 and SK-MEL-28, and female C57BL/6 mice were used for the study. Our in-vitro data showed that significant synergistic effects were obtained when celecoxib was used together with various concentrations of DTIC. A study with B16-F10 cells using flow cytometry analysis showed that the drug combination induced significantly more apoptosis than each drug used individually. Our in-vivo results showed that the drug combination was much more effective than each drug used alone for the inhibition of both melanoma growth and metastasis in the B16-F10+C57BL/6 mouse models. For melanoma growth, the median survival rates for phosphate-buffered saline (PBS) (control), celecoxib (30 mg/kg), DTIC-1 (10 mg/kg), DTIC-2 (positive control, 50 mg/kg), and the drug combination (DTIC 10 mg/kg+celecoxib 30 mg/kg) were 6, 6.5, 7.5, 7.5, and 9 days, respectively. For melanoma metastasis, the average number of metastatic tumors in murine lungs was 53.7±10.7, 31.8±18.6, 21.2±21.7, 7.0±9.0, and 0.8±2.0 for PBS, DTIC-1, celecoxib, the drug combination, and DTIC-2. Our results warrant further investigation of the combination as an effective treatment for melanoma patients.

Clinical pharmacology of ibuprofen and indomethacin in preterm infants with patent ductus arteriosus.

PubMed

Pacifici, Gian Maria

2014-01-01

Ibuprofen and indomethacin are potent non-selective cyclo-oxygenase inhibitors and inhibit prostaglandin E2 synthesis. The patent ductus arteriosus (PDA) occurs in more than 70% of preterm infants weighing <1500 g. Prostaglandin E2 relaxes smooth muscle, tends to inhibit the closure of PDA, yields vasodilatation of the afferent renal arterioles and maintains glomerular filtration rate (GFR). Ibuprofen and indomethacin inhibiting prostaglandin E2 synthesis close PDA and reduce GFR with consequent decrease of urine output and increase of serum creatinine concentrations. The aims of this study are to give the definitive estimates of PDA closure rate following ibuprofen or indomethacin treatment and to evaluate the extent of renal side effects following the administration of these drugs to preterm infants. Other aims are to review the metabolism and the pharmacokinetics of ibuprofen and indomethacin in preterm infants with PDA. The bibliographic search was performed using PubMed and EMBASE databases as search engines, January 2013 was the cutoff point. The %PDA closed by ibuprofen (n=24) and indomethacin (n=24) is 77.7±14.1 and 77.3±11.0, respectively. For ibuprofen, the gestational age of the infants included in the study ranged from 25.0 to 39.0 weeks (mean±SD=29.3±3.1 weeks). The %PDA did not correlate with the gestational age (p=0.2516). For indomethacin, the gestational age of infants included in the study ranged from 25.0 and 39.0 weeks (mean±SD=29.4±2.9 weeks). The %PDA did not correlate with the gestational age (p=0.3742). The treatment with ibuprofen reduces the urine output and increases the serum creatinine concentrations less extensively than indomethacin. The half-life (t1/2) of ibuprofen and indomethacin is lengthened and the clearance is reduced in preterm infants as compared with fullterm infants. Ibuprofen and indomethacin are equally effective in closing PDA. Treatment with ibuprofen decreases the risk of renal failure. Ibuprofen has the most

Augmented chondroprotective effect of coadministration of celecoxib and rebamipide in the monosodium iodoacetate rat model of osteoarthritis.

PubMed

Moon, Su-Jin; Park, Jin-Sil; Jeong, Jeong-Hee; Yang, Eun-Ji; Park, Mi-Kyung; Kim, Eun-Kyung; Park, Sung-Hwan; Kim, Ho-Youn; Cho, Mi-La; Min, Jun-Ki

2013-01-01

Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive loss of articular cartilage and chronic pain. Although cyclooxygenase-2 (COX-2) inhibitors such as celecoxib are recommended to patients at high risk of gastrointestinal (GI) adverse events, COX-2 inhibitors do not completely prevent GI adverse events. Rebamipide, a gastroprotective agent, has anti-inflammatory properties and acts as an oxygen radical scavenger. The aim of this study was to investigate the in vivo effects of coadministration of rebamipide and celecoxib in an OA rat model. OA was induced by intra-articular injection of monosodium iodoacetate. Oral administration of rebamipide was initiated on the day of OA induction. In this study, rebamipide showed antinociceptive properties and attenuated cartilage degeneration. Rebamipide reduced the expression of matrix metalloproteinase 13, interleukin-1β, inducible nitric oxide synthase, and nitrotyrosine in OA cartilage. OA rats treated with celecoxib in combination with rebamipide demonstrated a higher pain threshold than those treated with monotherapy. Histological examination also showed that the joints from OA animals treated with combination therapy demonstrated less cartilage damage than those of animals treated with monotherapy. We showed that the potential benefit of combination therapy with celecoxib and rebamipide on pain and cartilage degeneration in OA.

Impact of surfactants on the crystallization of aqueous suspensions of celecoxib amorphous solid dispersion spray dried particles.

PubMed

Chen, Jie; Ormes, James D; Higgins, John D; Taylor, Lynne S

2015-02-02

Amorphous solid dispersions are frequently prepared by spray drying. It is important that the resultant spray dried particles do not crystallize during formulation, storage, and upon administration. The goal of the current study was to evaluate the impact of surfactants on the crystallization of celecoxib amorphous solid dispersions (ASD), suspended in aqueous media. Solid dispersions of celecoxib with hydroxypropylmethylcellulose acetate succinate were manufactured by spray drying, and aqueous suspensions were prepared by adding the particles to acidified media containing various surfactants. Nucleation induction times were evaluated for celecoxib in the presence and absence of surfactants. The impact of the surfactants on drug and polymer leaching from the solid dispersion particles was also evaluated. Sodium dodecyl sulfate and Polysorbate 80 were found to promote crystallization from the ASD suspensions, while other surfactants including sodium taurocholate and Triton X100 were found to inhibit crystallization. The promotion or inhibition of crystallization was found to be related to the impact of the surfactant on the nucleation behavior of celecoxib, as well as the tendency to promote leaching of the drug from the ASD particle into the suspending medium. It was concluded that surfactant choice is critical to avoid failure of amorphous solid dispersions through crystallization of the drug.

LY3127760, a Selective Prostaglandin E4 (EP4) Receptor Antagonist, and Celecoxib: A Comparison of Pharmacological Profiles.

PubMed

Jin, Yan; Smith, Claire; Hu, Leijun; Coutant, David E; Whitehurst, Kelly; Phipps, Krista; McNearney, Terry Ann; Yang, Xiao; Ackermann, Bradley; Pottanat, Thomas; Landschulz, William

2018-01-01

Safety, tolerability, and pharmacology profiles of LY3127760, an EP4 antagonist, were explored in healthy subjects in a subject/investigator-blind, parallel-group, multiple-ascending dose study. Cohorts consisted of 13 patients randomized to LY3127760, celecoxib (400 mg), or placebo (9:2:2 ratio) for 28 days. LY3127760 was well tolerated; the most commonly observed adverse events were gastrointestinal, similar to celecoxib. LY3127760 increased release of ex vivo tumor necrosis factor alpha after lipopolysaccharide/prostaglandin E2 stimulation when compared with placebo, suggesting a dose-dependent blockade of the EP4 receptor. Compared with placebo, 24-h urinary excretion of prostaglandin E metabolite was modestly increased; prostacyclin metabolite was inhibited; and thromboxane A2 metabolite was unchanged. Effects on sodium and potassium excretion were similar to those of celecoxib. We conclude that LY3127760 demonstrated similar effects on prostacyclin synthesis and renal sodium retention as celecoxib. These data support exploration of LY3127760 at daily doses of 60 mg to 600 mg in phase II trials. This trial's registration number: NCT01968070. © 2017 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

A dose ranging study of ibuprofen suspension as an antipyretic.

PubMed Central

Marriott, S C; Stephenson, T J; Hull, D; Pownall, R; Smith, C M; Butler, A

1991-01-01

A double blind trial was conducted to determine the dose of ibuprofen suspension, which is effective in reducing the body temperature. The principal measure of efficacy was a reduction in axillary temperature of 1 degree C or more three hours after dosing. A second objective of the trial was to compare the incidence and severity of side effects and the palatability of a range of ibuprofen doses. Ninety three children were included in the analysis. All four doses of ibuprofen studied (0.625 mg/kg-5 mg/kg) were associated with temperature reduction and only the lowest dose failed to satisfy the principal measure of efficacy. The influence of dose on the magnitude of the body temperature reduction was significant and the 5 mg/kg dose achieved the largest mean reduction in body temperature (2 degrees C). The tolerability and palatability of all doses studied were excellent. These findings suggest that ibuprofen is a good alternative to paracetamol as an antipyretic. PMID:1929509

Ryegrass uptake of carbamazepine and ibuprofen applied by urine fertilization.

PubMed

Winker, Martina; Clemens, Joachim; Reich, Margrit; Gulyas, Holger; Otterpohl, Ralf

2010-03-15

Human urine is a potential alternative fertilizer for agriculture. However, its usage is associated with a risk of spreading pharmaceutical residues to fields. The individual and combined behavior of carbamazepine and ibuprofen was investigated by GC/MS analysis in a greenhouse experiment using ryegrass fertilized with pharmaceutical-spiked urine. Only carbamazepine could be detected in soil, roots, and aerial plant parts. Fifty-three per cent of carbamazepine originally present in the urine was recovered in soil samples taken after three months. Additionally, 34% of carbamazepine was found in aerial plant parts and 0.3% in roots. Model calculations showed that neither roots nor Casparian strip posed a considerable barrier to uptake. Carbamazepine transport was clearly driven by transpiration. Ibuprofen was not detected in the soil or in any plant parts after three months. This was assumed to be due to biodegradation of ibuprofen. Carbamazepine and ibuprofen, singly or in combination, did not adversely affect the growth of ryegrass.

Rofecoxib versus ibuprofen for acute treatment of migraine: a randomised placebo controlled trial

PubMed Central

Misra, U; Jose, M; Kalita, J

2004-01-01

Background: Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long duration of action. Its role in migraine has not been systematically evaluated. Aim: To study the efficacy of rofecoxib in migraine. Method: In a randomised placebo controlled trial rofecoxib 25 mg, ibuprofen 400 mg, and placebo were compared regarding their efficacy in relieving acute migraine attack. Migraine patients with 2–6 attacks per month were recruited. Headache severity, functional disability, and severity of associated symptoms were graded on a 0–3 scale. The primary endpoint was pain relief at two hours. Relief of associated symptoms and sustained pain relief for 24 hours were also noted. Result: One hundred and twenty four patients were randomised into rofecoxib (42), ibuprofen (40), and placebo (42) groups. One hundred and one patients were followed up: 33 on rofecoxib, 35 ibuprofen, and 33 placebo. Patients' ages ranged from 16–62 (mean 31.4) years, and 83 were females. Pain relief at two hours was noted in 45.5% on rofecoxib, 55.6% on ibuprofen, and 9.1% in the placebo group. The associated symptoms at two hours were reduced in 39.4% on rofecoxib, 50% on ibuprofen, and 9.1% in the placebo group. Sustained 24 hour pain relief was noted in 36.4% on rofecoxib, 41% on ibuprofen, and 6.1% in the placebo group. In the ibuprofen group, five patients had abdominal pain but there were no side effects in those on rofecoxib or in the control group. Both rofecoxib and ibuprofen were significantly effective in relieving pain, associated symptoms at two hours, and in sustained pain relief. There was no significant difference between rofecoxib and ibuprofen in aborting acute migraine attacks. Conclusions: Both ibuprofen and rofecoxib were superior to placebo in aborting an acute migraine attack, and there was no significant difference in their efficacy in an acute migraine attack. PMID:15579612

Pharmacological assessment of ibuprofen arginate on platelet aggregation and colon cancer cell killing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ahmetaj-Shala, B., E-mail: b.ahmetaj@imperial.ac.uk; Tesfai, A.; Constantinou, C.

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, are amongst the most commonly used medications and produce their anti-inflammatory and analgesic benefits by blocking cyclooxygenase (COX)-2. These drugs also have the potential to prevent and treat cancer and some members of the class including ibuprofen can produce anti-platelet effects. Despite their utility, all NSAIDs are associated with increased risk of cardiovascular side effects which our recent work suggests could be mediated by increased levels of the endogenous NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) leading to reduced endothelial NOS activity and associated endothelial cell dysfunction. ADMA is a cardiotoxic hormone and biomarkermore » of cardiovascular risk whose effects can be prevented by L-arginine. The ibuprofen salt, ibuprofen arginate (Spididol{sup ®}) was created to increase drug solubility but we have previously established that it not only effectively blocks COX-2 but also provides an arginine source able to reverse the effects of ADMA in vitro and in vivo. Here we have gone on to explore whether the formulation of ibuprofen with arginine influences the potency and efficacy of the parent molecule using a range of simple in vitro assays designed to test the effects of NSAIDs on (i) platelet aggregation and (iii) colon cancer cell killing. Our findings demonstrate that ibuprofen arginate retains these key functional effects of NSAIDs with similar or increased potency compared to ibuprofen sodium, further illustrating the potential of ibuprofen arginate as an efficacious drug with the possibility of improved cardiovascular safety. - Highlights: • Arginine salts of ibuprofen have improved solubility and deliver arginine. • They retain full anti-inflammatory, anti-cancer and anti-platelet activity. • Arginine formulations may provide a safer but still efficacious NSAID therapy.« less

Celecoxib as adjunctive treatment to risperidone in children with autistic disorder: a randomized, double-blind, placebo-controlled trial.

PubMed

Asadabadi, Mahtab; Mohammadi, Mohammad-Reza; Ghanizadeh, Ahmad; Modabbernia, Amirhossein; Ashrafi, Mandana; Hassanzadeh, Elmira; Forghani, Saeedeh; Akhondzadeh, Shahin

2013-01-01

Autism is associated with activation of the inflammatory response system. This study aims to assess the efficacy of a cyclooxygenase-2 inhibitor, celecoxib, as adjunctive therapy in the treatment of autism In a 10-week randomized double-blind placebo-controlled study, 40 outpatient children with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision clinical diagnosis of autism were randomly allocated to celecoxib plus risperidone or placebo plus risperidone. The dose of risperidone and celecoxib were titrated up to 3 and 300 mg/day, respectively. Patients were assessed at baseline and after 2, 4, 6, and 10 weeks of starting medication using the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Primary outcome measure was the change in irritability subscale of ABC-C. Significant time × treatment interaction was observed for Irritability (F (1.658, 63.021) = 13.580, P < 0.001), Lethargy/Social Withdrawal (F (1.948, 74.032) = 16.811, P < 0.001), and Stereotypic Behavior (F(1.742, 66.198) = 12.104, P < 0.001), but not for Hyperactivity/Noncompliance (F (2.564, 97.424) = 1.469, P = 0.232), and Inappropriate Speech subscales (F (1.607, 61.075) = 0.173, P = 0.794). By week 10, patients in the celecoxib group showed significantly greater improvement in the Irritability (P < 0.001), Lethargy/Social Withdrawal (P < 0.001), and Stereotypic Behavior (P < 0.00) but not in Hyperactivity/Noncompliance (P = 0.202) and Inappropriate Speech (P = 0.802) subscales than the placebo group. Complete response was achieved by four (20 %) patients in the placebo group and 11 (55 %) patients in the celecoxib group (χ (2) (1) = 5.227, P = 0.022). Frequency of side effects was similar between the two groups. Combination of risperidone and celecoxib was superior to risperidone alone in treating irritability, social withdrawal, and stereotypy of children with autism. (Registration

Ibuprofen Differentially Affects Supraspinatus Muscle and Tendon Adaptations to Exercise in a Rat Model.

PubMed

Rooney, Sarah Ilkhanipour; Baskin, Rachel; Torino, Daniel J; Vafa, Rameen P; Khandekar, Pooja S; Kuntz, Andrew F; Soslowsky, Louis J

2016-09-01

Previous studies have shown that ibuprofen is detrimental to tissue healing after acute injury; however, the effects of ibuprofen when combined with noninjurious exercise are debated. Administration of ibuprofen to rats undergoing a noninjurious treadmill exercise protocol will abolish the beneficial adaptations found with exercise but will have no effect on sedentary muscle and tendon properties. Controlled laboratory study. A total of 167 male Sprague-Dawley rats were divided into exercise or cage activity (sedentary) groups and acute (a single bout of exercise followed by 24 hours of rest) and chronic (2 or 8 weeks of repeated exercise) response times. Half of the rats were administered ibuprofen to investigate the effects of this drug over time when combined with different activity levels (exercise and sedentary). Supraspinatus tendons were used for mechanical testing and histologic assessment (organization, cell shape, cellularity), and supraspinatus muscles were used for morphologic (fiber cross-sectional area, centrally nucleated fibers) and fiber type analysis. Chronic intake of ibuprofen did not impair supraspinatus tendon organization or mechanical adaptations (stiffness, modulus, maximum load, maximum stress, dynamic modulus, or viscoelastic properties) to exercise. Tendon mechanical properties were not diminished and in some instances increased with ibuprofen. In contrast, total supraspinatus muscle fiber cross-sectional area decreased with ibuprofen at chronic response times, and some fiber type-specific changes were detected. Chronic administration of ibuprofen does not impair supraspinatus tendon mechanical properties in a rat model of exercise but does decrease supraspinatus muscle fiber cross-sectional area. This fundamental study adds to the growing literature on the effects of ibuprofen on musculoskeletal tissues and provides a solid foundation on which future work can build. The study findings suggest that ibuprofen does not detrimentally affect

Tomography-guided palisade sacroiliac joint radiofrequency neurotomy versus celecoxib for ankylosing spondylitis: a open-label, randomized, and controlled trial.

PubMed

Zheng, Yongjun; Gu, Minghong; Shi, Dongping; Li, Mingli; Ye, Le; Wang, Xiangrui

2014-09-01

Sacroiliac joint (SIJ) pain is a common symptom in ankylosing spondylitis (AS). Palisade sacroiliac joint radiofrequency neurotomy (PSRN) is a novel treatment for the SIJ pain. In the current clinical trial, we treated AS patients with significant SIJ pain using PSRN under computed tomography guidance and compared the results with the celecoxib treatment. The current study included 155 AS patients. Patients were randomly assigned to receive PSRN or celecoxib treatment (400 mg/day for 24 weeks). The primary endpoint was global pain intensity in visual analog scale, at week 12. Secondary endpoints included pain intensity at week 24, disease activity, functional and mobility capacities, and adverse events at week 24. In comparison with the baseline collected immediately prior to the interventions, global pain intensity was significantly lower at both 12 and 24 weeks after the treatment in both arms. Pain reduction was more robust in the PSRN arm (by more than 1.9 and 2.2 cm at 12 and 24 weeks in comparison with the celecoxib arm, P < 0.0001 for both). The PSRN was also more effective in improving physical function and spinal mobility (P < 0.05 vs. celecoxib for both). Gastrointestional irritation was more frequent in the celecoxib arm than in the PSRN arm (P < 0.05). No severe complications were noted in either arm. PSRN is both efficacious and safe in managing SIJ pain in patients with AS.

Fisher Discrimination of Metabolic Changes in Rats Treated with Aspirin and Ibuprofen.

PubMed

Zhang, Jing; Song, Huanchun; Jiang, Shuying; Chen, Zhibin; Tong, Shuhua; Lin, Feiyan; Wen, Congcong; Zhang, Xiuhua; Hu, Lufeng

2017-01-01

Aspirin and ibuprofen are the most frequently prescribed non-steroidal anti-inflammatory drugs in the world. However, both are associated with a variety of toxicities. We applied serum metabonomics and Fisher discrimination for the early diagnosis of its toxic reaction in order to help diagnose these toxicities. A total of 45 rats were randomly divided into Control group, Aspirin group, and Ibuprofen groups. The experiment groups were given intragastric aspirin (15 mg/kg) or ibuprofen (15 mg/kg) for 3 weeks. Liver function tests were performed and blood metabonomics were analyzed by gas chromatography-mass spectrometry. The most important compounds altered were trihydroxybutyric acid and l-alanine in the aspirin group, and acetoacetic acid, l-alanine, and trihydroxybutyric acid in the ibuprofen group. With respect to metabolic profiles, all 3 groups were completely distinct from one another. Fisher discrimination showed that 91.1% of the original grouped cases were correctly classified by the third week. However, only 55.6% of liver function tests were able to classify grouped cases correctly. Trihydroxybutyric acid, l-alanine, and acetoacetic acid were the most significant indicators of altered serum metabolites following intragastric administration of aspirin and ibuprofen in rates. These metabolomic data may be used for classification of aspirin and ibuprofen toxicity. © 2017 S. Karger AG, Basel.

Ibuprofen-Mediated Reversal of Fluconazole Resistance in Clinical Isolates of Candida

PubMed Central

Sharma, Monika; Kotwal, Aarti; Thakuria, Bhaskar; Kakati, Barnali; Chauhan, Bhupendra Singh; Patras, Abhishek

2015-01-01

Introduction: In view of the increasing prevalence of invasive Candidiasis in today’s health-care scenario and the emergence of fluconazole resistance among clinical isolates of Candida, we sought to determine if Ibuprofen could elicit a reversal of fluconazole resistance and thereby offer a potential therapeutic breakthrough in fluconazole-resistant Candidiasis. Materials and Methods: We selected 69 clinical isolates of Candida, which demonstrated an MIC of >32 μg/ml for fluconazole, and subjected them to broth microdilution in presence and absence of Ibuprofen. Results: Forty two of the 69 isolates (60.9%) demonstrated reversal of Fluconazole resistance with concomitant use of Ibuprofen. This was characterized by significant species-wise variation (p=0.00008), with all the C. albicans isolates and none of the C. glabrata isolates demonstrating such reversal. Only 22.2% and 37.7% of C. krusei and C. tropicalis isolates respectively showed Ibuprofen-mediated reversal of Fluconazole resistance. Conclusion: Since Ibuprofen is a known efflux pump inhibitor, our findings hint at the possible mechanism of Fluconazole resistance in most of our Candida isolates and suggest a potential therapeutic alternative that could be useful in the majority of Fluconazole-resistant clinical isolates of Candida. PMID:25737988

The IPSO study: ibuprofen, paracetamol study in osteoarthritis. A randomised comparative clinical study comparing the efficacy and safety of ibuprofen and paracetamol analgesic treatment of osteoarthritis of the knee or hip

PubMed Central

Boureau, F; Schneid, H; Zeghari, N; Wall, R; Bourgeois, P

2004-01-01

Objective: To compare the analgesic efficacy of single and multiple doses of ibuprofen with that of paracetamol in patients with knee or hip osteoarthritis (IPSO study). Method: 222 patients were randomised in a double blind, multicentre study—156 (70%) had a painful knee joint and 66 (30%) a painful hip joint. The main efficacy criterion was pain intensity assessment after a single dose (ibuprofen 400 mg, paracetamol 1000 mg). Functional disability assessment and patient global assessment were carried out over 14 days. Results: The sum of the pain intensity difference over 6 hours after the first administration was significantly higher (p = 0.046) in the ibuprofen group than in the paracetamol group. Over 14 days pain intensity decreased from the first day and was significantly lower in the ibuprofen group than in the paracetamol group (p<0.05). The functional disability of the patient was assessed using the WOMAC; the ibuprofen group improved significantly over 2 weeks compared with the paracetamol group for each of the subscales: stiffness (p<0.002), pain (p<0.001), physical function (p<0.002). The drugs were equally safe. Conclusion: The IPSO study shows that for the treatment of osteoarthritic pain, ibuprofen 400 mg at a single and multiple dose (1200 mg/day) for 14 days is more effective than paracetamol, either as a single dose of 1000 mg or a multiple dose (3000 mg/day). Because ibuprofen and paracetamol have similar tolerability, this study indicates that the efficacy/tolerability ratio of ibuprofen is better than that of paracetamol in this indication over 14 days. PMID:15308513

Effect of pH and Ibuprofen on Phopholipid Bilayer Bending Modulus

NASA Astrophysics Data System (ADS)

Boggara, Mohan; Faraone, Antonio; Krishnamoorti, Ramanan

2010-03-01

Non-steroidal anti-inflammatory drugs (NSAIDs) e.g. Aspirin and Ibuprofen, are known to cause gastrointestinal (GI) toxicity with chronic usage. However, NSAIDs pre-associated with phospholipids has been experimentally shown to reduce the GI toxicity and increase the therapeutic efficacy. In this study, using neutron spin-echo the effect of ibuprofen on the phospholipid membrane bending modulus is studied as a function of pH and temperature. Ibuprofen was found to lower the bending modulus at all pH values. We further present molecular insights into the observed effect on membrane dynamics based on structural studies using molecular dynamics simulations and small angle neutron scattering data as well as changes in zwitterionic headgroup electrostatics due to pH and addition of ibuprofen. This study is expected to help towards effective design of drug delivery nanoparticles based on variety of soft condensed matter such as lipids or polymers.

Ibuprofen-associated acute kidney injury in dehydrated children with acute gastroenteritis.

PubMed

Balestracci, Alejandro; Ezquer, Mauricio; Elmo, María Eugenia; Molini, Andrea; Thorel, Claudia; Torrents, Milagros; Toledo, Ismael

2015-10-01

Non-steroidal anti-inflammatory drugs (NSAIDs) induce acute kidney injury (AKI) in volume-depleted patients; however the prevalence of this complication is likely underestimated. We assessed the impact of ibuprofen exposure on renal function among dehydrated children with acute gastroenteritis (AGE) to further characterize NSAID-associated AKI. Over a 1-year period dehydrated children with AGE (n = 105) were prospectively enrolled and grouped as cases, presenting with AKI (n = 46) or controls, not presenting with AKI (n = 59). AKI was defined by pediatric RIFLE (pRIFLE) criteria. Among the children enrolled in the study, AKI prevalence was 44 %, and 34 (54 %) of the 63 patients who received ibuprofen developed renal impairment. Relative to the controls, children presenting with AKI were younger (median age 0.66 vs. 1.74 years; p < 0.001) and received ibuprofen more frequently (74 vs. 49 %, p = 0.01). After adjusting for the degree of dehydration, ibuprofen exposure remained an independent risk factor for AKI (p < 0.001, odds ratio 2.47, 95 % confidence interval 1.78-3.42). According to the pRIFLE criteria, 17 patients were at the 'risk' stage of AKI severity, 24 were at the 'injury' stage, and five were at the 'failure' stage; none required dialysis. Distribution of patients within categories was similar regardless of ibuprofen exposure. All cases fulled recovered from AKI. Ibuprofen-associated AKI was 54 % in our cohort of dehydrated children with AGE. Drug exposure increased the risk for developing AKI by more than twofold, independent of the magnitude of the dehydration.

Gastrointestinal safety and tolerance of ibuprofen at maximum over-the-counter dose.

PubMed

Doyle, G; Furey, S; Berlin, R; Cooper, S; Jayawardena, S; Ashraf, E; Baird, L

1999-07-01

Delineation of non-steroidal anti-inflammatory drug (NSAID) gastrointestinal toxicity has largely depended on retrospective epidemiologic studies which demonstrate that lower doses of NSAIDs pose a lower risk of gastrointestinal toxicity. Ibuprofen, a propionic acid NSAID, has, in most such studies, exhibited a favourable profile in terms of gastrointestinal bleeding. Since 1984, ibuprofen has been available as a non-prescription analgesic/antipyretic with a limit of 1200 mg/day for 10 days of continuous use. Trials and spontaneously reported adverse experiences suggest that gastrointestinal symptoms and bleeding are rare. This study prospectively evaluated the gastrointestinal tolerability, as compared to placebo, of the maximum non-prescription dose and duration of ibuprofen use in healthy subjects representative of a non-prescription analgesic user population. Gastrointestinal adverse experiences were similar in the placebo and ibuprofen groups (67 out of 413, 16% with placebo vs. 161 out of 833, 19% with ibuprofen). There was no difference between the two groups in the proportion discontinuing due to a gastrointestinal event. Gastrointestinal adverse experiences reported by >/= 1% of subjects were: dyspepsia, abdominal pain, nausea, diarrhoea, flatulence, and constipation. Seventeen (1.4%) subjects had positive occult blood tests: their frequency was comparable between treatments. When used as directed to treat episodic pain, non-prescription ibuprofen at the maximum dose of 1200 mg/day for 10 days, is well-tolerated.

Impact of oral versus intravenous ibuprofen on neurodevelopmental outcome: a randomized controlled parallel study.

PubMed

Eras, Zeynep; Gokmen, Tulin; Erdeve, Omer; Ozyurt, Banu Mutlu; Saridas, Bagdagul; Dilmen, Ugur

2013-11-01

Although neurodevelopmental outcomes related to the management of patent ductus arteriosus with intravenous indomethacin and ibuprofen are known, little data on the long-term effects of oral ibuprofen can be found in the literature. A follow-up study of 99 infants with birth weight ≤ 1,500 g and gestational age ≤ 32 weeks who received either oral or intravenous ibuprofen for patent ductus arteriosus was conducted to assess at 18 to 24 months (corrected age), abnormal neurological, neurosensory, and cognitive impairment were defined as follows:neurological outcomes included moderate/severe cerebral palsy, neurosensory outcomes included bilateral hearing loss and blindness in either eye, and cognitive impairment included mental developmental index score < 70. The 18- to 24-month (corrected age) long-term outcomes of 30 subjects who received oral ibuprofen were compared with 27 subjects who received intravenous ibuprofen by certified and experienced examiners who were blind to the definitions of the groups. The results revealed that the long-term outcomes of the treatment regimens did not significantly differ. Preterm infants who were treated with oral ibuprofen for patent ductus arteriosus had similar neurological, neurosensory, and cognitive outcomes to patients who received intravenous ibuprofen at 2 years of age. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Combined chondroitin sulfate and glucosamine for painful knee osteoarthritis: a multicentre, randomised, double-blind, non-inferiority trial versus celecoxib

PubMed Central

Hochberg, Marc C; Martel-Pelletier, Johanne; Monfort, Jordi; Möller, Ingrid; Castillo, Juan Ramón; Arden, Nigel; Berenbaum, Francis; Blanco, Francisco J; Conaghan, Philip G; Doménech, Gema; Henrotin, Yves; Pap, Thomas; Richette, Pascal; Sawitzke, Allen; du Souich, Patrick; Pelletier, Jean-Pierre

2016-01-01

Objectives To compare the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain. Methods Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA (MOVES) conducted in France, Germany, Poland and Spain evaluating treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2–3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0–500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D. Results The adjusted mean change (95% CI) in WOMAC pain was −185.7 (−200.3 to −171.1) (50.1% decrease) with CS+GH and −186.8 (−201.7 to −171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of −40: −1.11 (−22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were low and similarly distributed between groups. Conclusions CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile. Trial

Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle.

PubMed

Hu, Liandong; Hu, Qiaofeng; Yang, Jianxue

2014-10-01

The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 µg/cm(2)/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen.

Periorbital edema associated with separate courses of ibuprofen and naproxen.

PubMed

Balas, Morad; Plakogiannis, Roda; Sinnett, Mark

2010-06-01

A case of periorbital edema associated with separate courses of ibuprofen and naproxen is reported. An 80-year-old African- American woman with a history of osteoarthritis and hypertension came to the clinic. Her medication regimen included fosinopril sodium 40 mg daily, which she began two years prior. She had no known drug allergies and denied consuming any over-the-counter medications or herbal substances and reported a negative atopic status. She had seen her primary care provider several days prior and reported pain in the hands, fingers, and ankles, which would escalate in the morning and progressively lessen during the course of the day. Her physician prescribed naproxen 375 mg every eight hours as needed. After ingesting two doses of naproxen, she developed itching, swelling, and erythema around the left eye that became progressively worse and spread to the right eye. She contacted her primary care physician, who instructed her to discontinue the naproxen, and the reaction resolved within three days. The patient was maintained on acetaminophen for the arthritic pain with no issues. Approximately three months prior, ibuprofen 600 mg every eight hours as needed was prescribed for the same pain. She stated that after ingesting two doses of ibuprofen, she experienced a reaction similar to that recently experienced with naproxen. At that time, she was instructed to discontinue the ibuprofen, and her symptoms resolved. An elderly woman developed periorbital edema after taking ibuprofen on one occasion and naproxen on another.

Celecoxib offsets the negative renal influences of cyclosporine via modulation of the TGF-β1/IL-2/COX-2/endothelin ET(B) receptor cascade.

PubMed

El-Gowelli, Hanan M; Helmy, Maged W; Ali, Rabab M; El-Mas, Mahmoud M

2014-03-01

Endothelin (ET) signaling provokes nephrotoxicity induced by the immunosuppressant drug cyclosporine A (CSA). We tested the hypotheses that (i): celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, counterbalances renal derangements caused by CSA in rats and (ii) the COX-2/endothelin ET(B) receptor signaling mediates the CSA-celecoxib interaction. Ten-day treatment with CSA (20 mg/kg/day) significantly increased biochemical indices of renal function (serum urea, creatinine), inflammation (interleukin-2, IL-2) and fibrosis (transforming growth factor-β₁, TGF-β₁). Histologically, CSA caused renal tubular atrophy along with interstitial fibrosis. These detrimental renal effects of CSA were largely reduced in rats treated concurrently with celecoxib (10 mg/kg/day). We also report that cortical glomerular and medullary tubular protein expressions of COX-2 and ET(B) receptors were reduced by CSA and restored to near-control values in rats treated simultaneously with celecoxib. The importance of ET(B) receptors in renal control and in the CSA-celecoxib interaction was further verified by the findings (i) most of the adverse biochemical, inflammatory, and histopathological profiles of CSA were replicated in rats treated with the endothelin ETB receptor antagonist BQ788 (0.1 mg/kg/day, 10 days), and (ii) the BQ788 effects, like those of CSA, were alleviated in rats treated concurrently with celecoxib. Together, the data suggest that the facilitation of the interplay between the TGF-β1/IL-2/COX-2 pathway and the endothelin ET(B) receptors constitutes the cellular mechanism by which celecoxib ameliorates the nephrotoxic manifestations of CSA in rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Ibuprofen-loaded poly(lactic-co-glycolic acid) films for controlled drug release.

PubMed

Pang, Jianmei; Luan, Yuxia; Li, Feifei; Cai, Xiaoqing; Du, Jimin; Li, Zhonghao

2011-01-01

Ibuprofen- (IBU) loaded biocompatible poly(lactic-co-glycolic acid) (PLGA) films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.

Ibuprofen for the treatment of patent ductus arteriosus in preterm or low birth weight (or both) infants.

PubMed

Ohlsson, Arne; Walia, Rajneesh; Shah, Sachin S

2015-02-18

Indomethacin is used as standard therapy to close a patent ductus arteriosus (PDA) but is associated with reduced blood flow to several organs. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin with fewer adverse effects. To determine the effectiveness and safety of ibuprofen compared with indomethacin, other cyclo-oxygenase inhibitor, placebo or no intervention for closing a patent ductus arteriosus in preterm, low birth weight, or preterm and low birth weight infants. We searched The Cochrane Library, MEDLINE, EMBASE, Clincialtrials.gov, Controlled-trials.com, and www.abstracts2view.com/pas in May 2014. Randomised or quasi-randomised controlled trials of ibuprofen for the treatment of a PDA in newborn infants. Data collection and analysis conformed to the methods of the Cochrane Neonatal Review Group. We included 33 studies enrolling 2190 infants.Two studies compared intravenous (iv) ibuprofen versus placebo (270 infants). In one study (134 infants) ibuprofen reduced the incidence of failure to close a PDA (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.51 to 0.99; risk difference (RD) -0.18, 95% CI -0.35 to -0.01; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% CI 3 to 100). In one study (136 infants), ibuprofen reduced the composite outcome of infant mortality, infants who dropped out, or infants who required rescue treatment (RR 0.58, 95% CI 0.38 to 0.89; RD -0.22, 95% CI -0.38 to -0.06; NNTB 5, 95% CI 3 to 17). One study (64 infants) compared oral ibuprofen with placebo and noted a significant reduction in failure to close a PDA (RR 0.26, 95% CI 0.11 to 0.62; RD -0.44, 95% CI -0.65 to -0.23; NNTB 2, 95% CI 2 to 4).Twenty-one studies (1102 infants) reported failure rates for PDA closure with ibuprofen (oral or iv) compared with indomethacin (oral or iv). There was no significant difference between the groups (typical RR 1.00, 95% CI 0.84 to 1.20; I(2) = 0%; typical RD 0.00, 95% CI -0.05 to 0.05; I

Antihyperalgesic/antinociceptive effects of ceftriaxone and its synergistic interactions with different analgesics in inflammatory pain in rodents.

PubMed

Stepanovic-Petrovic, Radica M; Micov, Ana M; Tomic, Maja A; Kovacevic, Jovana M; Boškovic, Bogdan D

2014-03-01

The β-lactam antibiotic ceftriaxone stimulates glutamate transporter GLT-1 expression and is effective in neuropathic and visceral pain models. This study examined the effects of ceftriaxone and its interactions with different analgesics (ibuprofen, celecoxib, paracetamol, and levetiracetam) in somatic and visceral pain models in rodents. The effects of ceftriaxone (intraperitoneally/intraplantarly), analgesics (orally), and their combinations were examined in the carrageenan-induced paw inflammatory hyperalgesia model in rats (n = 6-12) and in the acetic acid-induced writhing test in mice (n = 6-10). The type of interaction between ceftriaxone and analgesics was determined by isobolographic analysis. Pretreatment with intraperitoneally administered ceftriaxone (10-200 mg/kg per day) for 7 days produced a significant dose-dependent antihyperalgesia in the somatic inflammatory model. Acute administration of ceftriaxone, via either intraperitoneal (10-200 mg/kg) or intraplantar (0.05-0.2 mg per paw) routes, produced a significant and dose-dependent but less efficacious antihyperalgesia. In the visceral pain model, significant dose-dependent antinociception of ceftriaxone (25-200 mg/kg per day) was observed only after the 7-day pretreatment. Isobolographic analysis in the inflammatory hyperalgesia model revealed approximately 10-fold reduction of doses of both drugs in all examined combinations. In the visceral nociception model, more than 7- and 17-fold reduction of doses of both drugs was observed in combinations of ceftriaxone with ibuprofen/paracetamol and celecoxib/levetiracetam, respectively. Ceftriaxone exerts antihyperalgesia/antinociception in both somatic and visceral inflammatory pain. Its efficacy is higher after a 7-day pretreatment than after acute administration. The two-drug combinations of ceftriaxone and the nonsteroidal analgesics/levetiracetam have synergistic interactions in both pain models. These results suggest that ceftriaxone, particularly

Levetiracetam interacts synergistically with nonsteroidal analgesics and caffeine to produce antihyperalgesia in rats.

PubMed

Tomić, Maja A; Micov, Ana M; Stepanović-Petrović, Radica M

2013-11-01

Levetiracetam is a novel anticonvulsant with antihyperalgesic efficacy in inflammatory pain. Nonsteroidal analgesics and caffeine, as analgesic adjuvant, are widely used against inflammatory pain. This study characterized the manner in which levetiracetam interacts with analgesics (ibuprofen, celecoxib, and paracetamol) and caffeine to suppress hyperalgesia in a model of localized inflammation. Rat paw inflammation was induced by intraplantar carrageenan (.1 mL, 1%). Hyperalgesia and antihyperalgesic effects of levetiracetam (orally), analgesics (orally), and caffeine (intraperitoneally) alone and 2-drug combinations of levetiracetam with analgesics or caffeine were examined by a modified paw pressure test. The type of interaction between components was determined by isobolographic analysis or by analysis of the log dose-response curves for drug combination and drugs alone. Levetiracetam (10-200 mg/kg), ibuprofen (12.5-100 mg/kg), celecoxib (3.75-30 mg/kg), paracetamol (50-200 mg/kg), caffeine (15-100 mg/kg), and 2-drug combinations of levetiracetam with analgesics/caffeine produced a significant, dose-dependent reduction of inflammatory hyperalgesia. Isobolographic analysis revealed that levetiracetam exerts a synergistic interaction with analgesics, with approximately 7-, 9-, and 11-fold reduction of doses of both drugs in combination of levetiracetam with paracetamol, celecoxib, and ibuprofen, respectively. Analysis of the log dose-response curves for levetiracetam (1-50 mg/kg) in the presence of caffeine (10 mg/kg) and levetiracetam applied alone also revealed a synergistic interaction. Levetiracetam's ED50 in the presence of caffeine was reduced approximately 11-fold. The presented data suggest that 2-drug combinations of levetiracetam and nonsteroidal analgesics or caffeine could be useful in treatment of inflammatory pain. The efficacy and the adverse effects of those mixtures should be explored further in clinical settings. Copyright © 2013

Destruction of vasculogenic mimicry channels by targeting epirubicin plus celecoxib liposomes in treatment of brain glioma

PubMed Central

Ju, Rui-Jun; Zeng, Fan; Liu, Lei; Mu, Li-Min; Xie, Hong-Jun; Zhao, Yao; Yan, Yan; Wu, Jia-Shuan; Hu, Ying-Jie; Lu, Wan-Liang

2016-01-01

The efficacy of chemotherapy for brain glioma is restricted by the blood–brain barrier (BBB), and surgery or radiotherapy cannot eliminate the glioma cells because of their unique location. Residual brain glioma cells can form vasculogenic mimicry (VM) channels that can cause a recurrence of brain glioma. In the present study, targeting liposomes incorporating epirubicin and celecoxib were prepared and used for the treatment of brain glioma, along with the destruction of their VM channels. Evaluations were performed on the human brain glioma U87MG cells in vitro and on intracranial brain glioma-bearing nude mice. Targeting epirubicin plus celecoxib liposomes in the circulatory blood system were able to be transported across the BBB, and accumulated in the brain glioma region. Then, the liposomes were internalized by brain glioma cells and killed glioma cells by direct cytotoxic injury and the induction of apoptosis. The induction of apoptosis was related to the activation of caspase-8- and -3-signaling pathways, the activation of the proapoptotic protein Bax, and the suppression of the antiapoptotic protein Mcl-1. The destruction of brain glioma VM channels was related to the downregulation of VM channel-forming indictors, which consisted of MMP-2, MMP-9, FAK, VE-Cad, and VEGF. The results demonstrated that the targeting epirubicin plus celecoxib liposomes were able to effectively destroy the glioma VM channels and exhibited significant efficacy in the treatment of intracranial glioma-bearing nude mice. Therefore, targeting epirubicin plus celecoxib liposomes could be a potential nanostructured formulation to treat gliomas and destroy their VM channels. PMID:27042063

Evaporation Behavior and Characterization of Eutectic Solvent and Ibuprofen Eutectic Solution.

PubMed

Phaechamud, Thawatchai; Tuntarawongsa, Sarun; Charoensuksai, Purin

2016-10-01

Liquid eutectic system of menthol and camphor has been reported as solvent and co-solvent for some drug delivery systems. However, surprisingly, the phase diagram of menthol-camphor eutectic has not been reported previously. The evaporation behavior, physicochemical, and thermal properties of this liquid eutectic and ibuprofen eutectic solution were characterized in this study. Differential scanning calorimetry (DSC) analysis indicated that a eutectic point of this system was near to 1:1 menthol/camphor and its eutectic temperature was -1°C. The solubility of ibuprofen in this eutectic was 282.11 ± 6.67 mg mL(-1) and increased the drug aqueous solubility fourfold. The shift of wave number from Fourier transform infrared spectroscopy (FTIR) indicated the hydrogen bonding of each compound in eutectic mixture. The weight loss from thermogravimetric analysis of menthol and camphor related to the evaporation and sublimation, respectively. Menthol demonstrated a lower apparent sublimation rate than camphor, and the evaporation rate of eutectic solvent was lower than the sublimation rate of camphor but higher than the evaporation of menthol. The evaporation rate of the ibuprofen eutectic solution was lower than that of the eutectic solvent because ibuprofen did not sublimate. This eutectic solvent prolonged the ibuprofen release with diffusion control. Thus, the beneficial information for thermal behavior and related properties of eutectic solvent comprising menthol-camphor and ibuprofen eutectic solution was attained successfully. The rather low evaporation of eutectic mixture will be beneficial for investigation and tracking the mechanism of transformation from nanoemulsion into nanosuspension in the further study using eutectic as oil phase.

Phytoextraction, phytotransformation and rhizodegradation of ibuprofen associated with Typha angustifolia in a horizontal subsurface flow constructed wetland.

PubMed

Li, Yifei; Zhang, Jiefeng; Zhu, Guibing; Liu, Yu; Wu, Bing; Ng, Wun Jern; Appan, Adhityan; Tan, Soon Keat

2016-10-01

Widespread occurrence of trace pharmaceutical residues in aquatic environments is of great concerns due to the potential chronic toxicity of certain pharmaceuticals including ibuprofen on aquatic organisms even at environmental levels. In this study, the phytoextraction, phytotransformation and rhizodegradation of ibuprofen associated with Typha angustifolia were investigated in a horizontal subsurface flow constructed wetland system. The experimental wetland system consisted of a planted bed with Typha angustifolia and an unplanted bed (control) to treat ibuprofen-loaded wastewater (∼107.2 μg L(-1)). Over a period of 342 days, ibuprofen was accumulated in leaf sheath and lamina tissues at a mean concentration of 160.7 ng g(-1), indicating the occurrence of the phytoextraction of ibuprofen. Root-uptake ibuprofen was partially transformed to ibuprofen carboxylic acid, 2-hydroxy ibuprofen and 1-hydroxy ibuprofen which were found to be 1374.9, 235.6 and 301.5 ng g(-1) in the sheath, respectively, while they were 1051.1, 693.6 and 178.7 ng g(-1) in the lamina. The findings from pyrosequencing analysis of the rhizosphere bacteria suggest that the Dechloromonas sp., the Clostridium sp. (e.g. Clostridium saccharobutylicum), the order Sphingobacteriales, and the Cytophaga sp. in the order Cytophagales were most probably responsible for the rhizodegradation of ibuprofen. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of ibuprofen on cognition and NMDA receptor subunit expression across aging.

PubMed

Márquez Loza, Alejandra; Elias, Valerie; Wong, Carmen P; Ho, Emily; Bermudez, Michelle; Magnusson, Kathy R

2017-03-06

Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-d-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26months) were fed ibuprofen (375ppm) in NIH31 diet or diet alone for 6weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2' cassettes in the hippocampus. GluN1-3 splice form mRNA and C2' cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of Ibuprofen on Cognition and NMDA Receptor Subunit Expression Across Aging

PubMed Central

Loza, Alejandra Márquez; Elias, Valerie; Wong, Carmen P.; Ho, Emily; Bermudez, Michelle; Magnusson, Kathy R.

2017-01-01

Age-related declines in long- and short-term memory show relationships to decreases in N-methyl-D-aspartate (NMDA) receptor expression, which may involve inflammation. This study was designed to determine effects of an anti-inflammatory drug, ibuprofen, on cognitive function and NMDA receptor expression across aging. Male C57BL/6 mice (ages 5, 14, 20, and 26 months) were fed ibuprofen (375 ppm) in NIH31 diet or diet alone for 6 weeks prior to testing. Behavioral testing using the Morris water maze showed that older mice performed significantly worse than younger in spatial long-term memory, reversal, and short-term memory tasks. Ibuprofen enhanced overall performance in the short-term memory task, but this appeared to be more related to improved executive function than memory. Ibuprofen induced significant decreases over all ages in the mRNA densities for GluN2B subunit, all GluN1 splice variants, and GluN1-1 splice forms in the frontal cortex and in protein expression of GluN2A, GluN2B and GluN1 C2′ cassettes in the hippocampus. GluN1-3 splice form mRNA and C2′ cassette protein were significantly increased across ages in frontal lobes of ibuprofen-treated mice. Ibuprofen did not alter expression of pro-inflammatory cytokines IL-1β and TNFα, but did reduce the area of reactive astrocyte immunostaining in frontal cortex of aged mice. Enhancement in executive function showed a relationship to increased GluN1-3 mRNA and decreased gliosis. These findings suggest that inflammation may play a role in executive function declines in aged animals, but other effects of ibuprofen on NMDA receptors appeared to be unrelated to aging or inflammation. PMID:28057539

Celecoxib restores angiogenic factor expression at the maternal-fetal interface in the BPH/5 mouse model of preeclampsia.

PubMed

Reijnders, Dorien; Liu, Chin-Chi; Xu, Xinjing; Zhao, Anna M; Olson, Kelsey N; Butler, Scott D; Douglas, Nataki C; Sones, Jenny L

2018-05-01

Preeclampsia (PE), a hypertensive disease of pregnancy, is a leading cause of fetal and maternal morbidity/mortality. Early angiogenic and inflammatory disturbances within the placenta are thought to underlie the development of the maternal PE syndrome and poor pregnancy outcomes. However, the exact etiology remains largely unknown. Here, we use the BPH/5 mouse model of PE to elucidate the way in which inflammation early in pregnancy contributes to abnormal expression of angiogenic factors at the maternal-fetal interface. We have previously described improvement in maternal hypertension and fetal growth restriction in this model after treatment with the anti-inflammatory cyclooxygenase-2 (Cox2) specific inhibitor celecoxib. To further characterize the mechanisms by which celecoxib improves poor pregnancy outcomes in BPH/5 mice, we determined expression of angiogenic factors and complement pathway components after celecoxib. In BPH/5 implantation sites there was increased hypoxia inducible factor-1α ( Hif1α), heme oxygenase-1 ( Ho-1), and stem cell factor ( Scf) mRNA concomitant with elevated prostaglandin synthase 2 ( Ptgs2), encoding Cox2, and elevated VEGF protein. Angiopoietin 1 ( Ang1), tunica interna endothelial cell kinase-2 receptor ( Tie2), complement factor 3 ( C3), and complement factor B ( CfB) were increased in midgestation BPH/5 placentae. Whereas BPH/5 expression levels of VEGF, Ang1, and Tie2 normalized after celecoxib, placental C3 and CfB mRNA remained unchanged. However, celecoxib did reduce the pregnancy-specific circulating soluble fms-like tyrosine kinase-1 (sFlt-1) rise in BPH/5 mice at midgestation. These data show that elevated Cox2 during implantation contributes to placental angiogenic factor imbalances in the BPH/5 mouse model of PE.

Pilot monitoring study of ibuprofen in surface waters of north of Portugal.

PubMed

Paíga, Paula; Santos, Lúcia H M L M; Amorim, Célia G; Araújo, Alberto N; Montenegro, M Conceição B S M; Pena, Angelina; Delerue-Matos, Cristina

2013-04-01

Ibuprofen is amongst the most worldwide consumed pharmaceuticals. The present work presents the first data in the occurrence of ibuprofen in Portuguese surface waters, focusing in the north area of the country, which is one of the most densely populated areas of Portugal. Analysis of ibuprofen is based on pre-concentration of the analyte with solid phase extraction and subsequent determination with liquid chromatography coupled to fluorescence detection. A total of 42 water samples, including surface waters, landfill leachates, Wastewater Treatment Plant (WWTP), and hospital effluents, were analyzed in order to evaluate the occurrence of ibuprofen in the north of Portugal. In general, the highest concentrations were found in the river mouths and in the estuarine zone. The maximum concentrations found were 48,720 ng L(-1) in the landfill leachate, 3,868 ng L(-1) in hospital effluent, 616 ng L(-1) in WWTP effluent, and 723 ng L(-1) in surface waters (Lima river). Environmental risk assessment was evaluated and at the measured concentrations only landfill leachates reveal potential ecotoxicological risk for aquatic organisms. Owing to a high consumption rate of ibuprofen among Portuguese population, as prescribed and non-prescribed medicine, the importance of hospitals, WWTPs, and landfills as sources of entrance of pharmaceuticals in the environment was pointed out. Landfill leachates showed the highest contribution for ibuprofen mass loading into surface waters. On the basis of our findings, more studies are needed as an attempt to assess more vulnerable areas.

Ibuprofen for acute treatment of episodic tension-type headache in adults.

PubMed

Derry, Sheena; Wiffen, Philip J; Moore, R Andrew; Bendtsen, Lars

2015-07-31

Tension-type headache (TTH) affects about one person in five worldwide. It is divided into infrequent episodic TTH (fewer than one headache per month), frequent episodic TTH (1 to 14 headaches per month), and chronic TTH (15 headaches a month or more). Ibuprofen is one of a number of analgesics suggested for acute treatment of headaches in frequent episodic TTH. To assess the efficacy and safety of oral ibuprofen for treatment of acute episodic TTH in adults. We searched CENTRAL (The Cochrane Library), MEDLINE, EMBASE, and our own in-house database to January 2015. We sought unpublished studies by asking personal contacts and searching on-line clinical trial registers and manufacturers' websites. We included randomised, placebo-controlled studies (parallel-group or cross-over) using oral ibuprofen for symptomatic relief of an acute episode of TTH. Studies had to be prospective and include at least 10 participants per treatment arm. Two review authors independently assessed studies for inclusion, and extracted data. Numbers of participants achieving each outcome were used to calculate risk ratio (RR) and number needed to treat for an additional beneficial outcome (NNT) or number needed to treat for an additional harmful outcome (NNH) of oral ibuprofen compared to placebo for a range of outcomes, predominantly those recommended by the International Headache Society (IHS). We included 12 studies, all of which enrolled adult participants with frequent episodic TTH. Nine used the IHS diagnostic criteria, but two used the older classification of the Ad Hoc Committee, and one did not describe diagnostic criteria but excluded participants with migraines. While 3094 people with TTH participated in these studies, the numbers available for any form of analysis were lower than this; placebo was taken by 733, standard ibuprofen 200 mg by 127, standard ibuprofen 400 mg by 892, and fast-acting ibuprofen 400 mg by 230. Participants had moderate or severe pain at the start of

Safety profile: fifteen years of clinical experience with ibuprofen.

PubMed

Royer, G L; Seckman, C E; Welshman, I R

1984-07-13

Since its introduction in the United States in 1974, ibuprofen (Motrin, Upjohn) has been shown to be safe and effective for the treatment of pain, dysmenorrhea, inflammation, and fever. A careful review of pre-registration and postmarketing data from both patients and normal subjects clearly indicates ibuprofen's remarkable safety profile compared with that of aspirin and other commonly prescribed nonsteroidal anti-inflammatory agents. Continued safety can be anticipated on the basis of the past 15 years of review experience.

Enhancement of transdermal delivery of ibuprofen using microemulsion vehicle

PubMed Central

Hu, Liandong; Hu, Qiaofeng; Yang, Jianxue

2014-01-01

Objective(s): The objective of this study was to find a stable microemulsion vehicle for transdermal delivery of ibuprofen to improve the skin permeability. Materials and Methods: Microemulsion was prepared using different sorts of oils, surfactants and co-surfactants. Pseudo-ternary phase diagrams were used to evaluate the microemulsion domain. The effects of oleic acid and surfactant mixture on skin permeation of ibuprofen were evaluated with excised skins. Results: The optimum formulation F3 consisting of 6% oleic acid, 30% Cremophor RH40/Transcutol P (2:1, w/w) and 59% water phase, showed a high permeation rate of 42.98 µg/cm2/hr. The mean droplet size of microemulsion was about 43 nm and no skin irritation signs were observed on the skin of rabbits. Conclusion: These results indicated that this novel microemulsion is a useful formulation for the transdermal delivery of ibuprofen. PMID:25729544

Impregnation of Ibuprofen into Polycaprolactone using supercritical carbon dioxide

NASA Astrophysics Data System (ADS)

Yoganathan, Roshan; Mammucari, Raffaella; Foster, Neil R.

2010-03-01

Polycaprolactone (PCL) is a Food and Drug Administration (FDA) approved biodegradable polyester used in tissue engineering applications. Ibuprofen is an anti-inflammatory drug which has good solubility in supercritical CO2 (SCCO2). The solubility of CO2 in PCL allows for the impregnation of CO2-soluble therapeutic agents into the polymer via a supercritical fluid (SCF) process. Polymers impregnated with bio-active compounds are highly desired for medical implants and controlled drug delivery. In this study, the use of CO2 to impregnate PCL with ibuprofen was investigated. The effect of operating conditions on the impregnation of ibuprofen into PCL was investigated over two pressure and two temperature levels, 150bar and 200bar, 35°C and 40 °C, respectively. Polycaprolactone with drug-loadings as high as 27% w/w were obtained. Impregnated samples exhibited controlled drug release profiles over several days.

Celecoxib for the treatment of mild-to-moderate depression due to acute brucellosis: a double-blind, placebo-controlled, randomized trial.

PubMed

Jafari, S; Ashrafizadeh, S-G; Zeinoddini, A; Rasoulinejad, M; Entezari, P; Seddighi, S; Akhondzadeh, S

2015-08-01

Depression is a debilitating complication of brucellosis and how best to treat this is a matter of debate. Inflammatory processes are involved in the pathogenesis of both brucellosis and depression. Therefore, we hypothesized that celecoxib could be beneficial for the treatment of depression due to brucellosis. Forty outpatients with depression due to brucellosis with a Hamilton Depression Rating Scale score (HDRS) <19 participated in a randomized, double-blind, placebo-controlled trial and underwent 8 weeks of treatment with either celecoxib (200 mg bid) or placebo as an adjunctive to antibiotic therapy. Patients were evaluated using HDRS at baseline and weeks 4 and 8. Repeated-measures analysis demonstrated significant effect for time × treatment interaction on the HDRS score [F (1·43, 57·41) = 37·22, P < 0·001]. Significantly greater response to treatment occurred in the celecoxib group than in the placebo group at the study end [10 patients (50%) vs. no patient (0%), respectively, P < 0·001]. No serious adverse event was observed. Celecoxib is a safe and effective treatment for depression due to brucellosis when compared with placebo. © 2015 John Wiley & Sons Ltd.

Single‐dose pharmacokinetics of co‐crystal of tramadol–celecoxib: Results of a four‐way randomized open‐label phase I clinical trial in healthy subjects

PubMed Central

Lahjou, Mounia; Vaqué, Anna; Sust, Mariano; Encabo, Mercedes; Soler, Lluis; Sans, Artur; Sicard, Eric; Gascón, Neus; Encina, Gregorio; Plata‐Salamán, Carlos

2017-01-01

Aims Co‐crystal of tramadol–celecoxib (CTC) is a novel co‐crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E‐58425) and Mundipharma Research (MR308). This Phase I study compared single‐dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate‐release (IR) tramadol and celecoxib] alone and in open combination. Methods Healthy adults aged 18–55 years were orally administered four treatments under fasted conditions (separated by 7‐day wash‐out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment 1); 100 mg IR tramadol (Treatment 2); 100 mg celecoxib (Treatment 3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment 4). Treatment sequence was assigned using computer‐generated randomization. PK parameters were calculated using noncompartmental analysis with parameters for CTC adjusted according to reference product dose (100 mg). Results Thirty‐six subjects (28 male, mean age 36 years) participated. Tramadol PK parameters for Treatments‐1, –2 and –4, respectively, were 263, 346 and 349 ng ml–1 (mean maximum plasma concentration); 3039, 2979 and 3119 ng h ml–1 (mean cumulative area under the plasma concentration–time curve); and 2.7, 1.8 and 1.8 h (median time to maximum plasma concentration). For Treatments 1, 3 and 4, the respective celecoxib PK parameters were 313, 449 and 284 ng ml–1; 2183, 3093 and 2856 ng h ml–1; and 1.5, 2.3 and 3.0 h. No unexpected adverse events were reported. Conclusion PK parameters of each API in CTC were modified by co‐crystallization compared with marketed formulations of tramadol, celecoxib, and their open combination. PMID:28810061

Single-dose pharmacokinetics of co-crystal of tramadol-celecoxib: Results of a four-way randomized open-label phase I clinical trial in healthy subjects.

PubMed

Videla, Sebastián; Lahjou, Mounia; Vaqué, Anna; Sust, Mariano; Encabo, Mercedes; Soler, Lluis; Sans, Artur; Sicard, Eric; Gascón, Neus; Encina, Gregorio; Plata-Salamán, Carlos

2017-12-01

Co-crystal of tramadol-celecoxib (CTC) is a novel co-crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E-58425) and Mundipharma Research (MR308). This Phase I study compared single-dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate-release (IR) tramadol and celecoxib] alone and in open combination. Healthy adults aged 18-55 years were orally administered four treatments under fasted conditions (separated by 7-day wash-out period): 200 mg IR CTC (equivalent to 88 mg tramadol and 112 mg celecoxib; Treatment 1); 100 mg IR tramadol (Treatment 2); 100 mg celecoxib (Treatment 3); and 100 mg IR tramadol and 100 mg celecoxib (Treatment 4). Treatment sequence was assigned using computer-generated randomization. PK parameters were calculated using noncompartmental analysis with parameters for CTC adjusted according to reference product dose (100 mg). Thirty-six subjects (28 male, mean age 36 years) participated. Tramadol PK parameters for Treatments-1, -2 and -4, respectively, were 263, 346 and 349 ng ml -1 (mean maximum plasma concentration); 3039, 2979 and 3119 ng h ml -1 (mean cumulative area under the plasma concentration-time curve); and 2.7, 1.8 and 1.8 h (median time to maximum plasma concentration). For Treatments 1, 3 and 4, the respective celecoxib PK parameters were 313, 449 and 284 ng ml -1 ; 2183, 3093 and 2856 ng h ml -1 ; and 1.5, 2.3 and 3.0 h. No unexpected adverse events were reported. PK parameters of each API in CTC were modified by co-crystallization compared with marketed formulations of tramadol, celecoxib, and their open combination. © 2017 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

Inhibition of endocannabinoid metabolism by the metabolites of ibuprofen and flurbiprofen.

PubMed

Karlsson, Jessica; Fowler, Christopher J

2014-01-01

In addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) by cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH), respectively. Here, we investigated whether these effects upon endocannabinoid metabolism are shared by the main metabolites of ibuprofen and flurbiprofen. COX activities were measured via changes in oxygen consumption due to oxygenation of arachidonic acid (for COX-1) and arachidonic acid and 2-AG (for COX-2). FAAH activity was quantified by measuring hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at lower concentrations than the oxygenation of arachidonic acid was seen with 4'-hydroxyflurbiprofen and possibly also 3'-hydroxyibuprofen, albeit at lower potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites retained the ability to inhibit FAAH in a pH-dependent manner, although the potency was lower than seen with the parent compounds. It is concluded that the primary metabolites of ibuprofen and flurbiprofen retain some of the properties of the parent compound with respect to inhibition of endocannabinoid metabolism. However, these effects are unlikely to contribute to the actions of the parent compounds in vivo.

Inhibition of Endocannabinoid Metabolism by the Metabolites of Ibuprofen and Flurbiprofen

PubMed Central

Karlsson, Jessica; Fowler, Christopher J.

2014-01-01

Background In addition to their effects upon prostaglandin synthesis, the non-steroidal anti-inflammatory drugs ibuprofen and flurbiprofen inhibit the metabolism of the endocannabinoids 2-arachidonoylglycerol (2-AG) and anandamide (AEA) by cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH), respectively. Here, we investigated whether these effects upon endocannabinoid metabolism are shared by the main metabolites of ibuprofen and flurbiprofen. Methodology/Principal Findings COX activities were measured via changes in oxygen consumption due to oxygenation of arachidonic acid (for COX-1) and arachidonic acid and 2-AG (for COX-2). FAAH activity was quantified by measuring hydrolysis of tritium labelled AEA in rat brain homogenates. The ability of ibuprofen and flurbiprofen to inhibit COX-2-catalysed oxygenation of 2-AG at lower concentrations than the oxygenation of arachidonic acid was seen with 4′-hydroxyflurbiprofen and possibly also 3′-hydroxyibuprofen, albeit at lower potencies than the parent compounds. All ibuprofen and flurbiprofen metabolites retained the ability to inhibit FAAH in a pH-dependent manner, although the potency was lower than seen with the parent compounds. Conclusions/Significance It is concluded that the primary metabolites of ibuprofen and flurbiprofen retain some of the properties of the parent compound with respect to inhibition of endocannabinoid metabolism. However, these effects are unlikely to contribute to the actions of the parent compounds in vivo. PMID:25061885

A Pharmacokinetic Study of an Ibuprofen Topical Patch in Healthy Male and Female Adult Volunteers.

PubMed

Lewis, Fraser; Connolly, Mark P; Bhatt, Aomesh

2018-01-11

The pharmacokinetics of a novel locally applied ibuprofen topical patch was evaluated. Healthy subjects (n = 28) were administered a 200-mg ibuprofen patch every 24 hours for 5 days, and steady-state pharmacokinetics was determined. The amount of ibuprofen remaining in the patch following each patch removal was also assessed. The maximum steady-state drug concentration and area under the concentration curve from time 0 on day 5 (t = 0) to the 24-hours sample on day 6 were 514 ng/mL (95% CI 439 to 603 ng/mL) and 9.78 kg·h/mL (95% CI 8.43 to 11.4 kg·h/mL), respectively. Maximum ibuprofen concentration on day 5 occurred at 20 hours post-patch application. No evidence of drug accumulation was observed, and steady state was achieved between days 2 and 5. Ibuprofen levels attenuated rapidly to baseline within 24 hours after treatment discontinuation. The amount of ibuprofen remaining in the patch was high (≥80%). Treatment-emergent adverse events were generally mild, with the most prevalent being headache (n = 6; 21.4%). Only 4 TEAEs were considered related to the ibuprofen patch: paresthesia (n = 1), headache (n = 2), and pruritic rash (n = 1). The study found that the systematic absorption of ibuprofen from a 200-mg patch was low and that the levels of ibuprofen leaving the patch over a 24-hour period are consistent with levels required for therapeutic relief as shown in other studies. © 2018, The American College of Clinical Pharmacology.

Prevention of peritendinous adhesions with electrospun ibuprofen-loaded poly(L-lactic acid)-polyethylene glycol fibrous membranes.

PubMed

Liu, Shen; Hu, Changmin; Li, Fengfeng; Li, Xu-jun; Cui, Wenguo; Fan, Cunyi

2013-02-01

Physical barriers are commonly used to reduce peritendinous adhesion after injury. However, the inflammatory response to surgery cannot be prevented. This study was designed to evaluate the ability of ibuprofen-loaded poly(l-lactic acid)-polyethylene glycol (PELA) diblock copolymer fibrous membranes in preventing adhesion formation and reduce inflammation. Electrospun PELA fibrous membranes underwent mechanical testing and were characterized by morphology, surface wettability, drug release, and degradation. Results of an in vitro drug release study showed that a burst release was followed by sustained release from fibrous membranes with high initial ibuprofen content. Fewer L929 mouse fibroblasts adhered to and proliferated on the ibuprofen-loaded PELA fibrous membrane compared with tissue culture plates or PELA fibrous membrane without ibuprofen. In a chicken model of flexor digitorum profundus tendon surgery, the ibuprofen-loaded PELA fibrous membranes prevented tissue adhesion and significantly reduced inflammation. Taken together, these results demonstrate that ibuprofen-loaded PELA fibrous membranes prevent peritendinous adhesion formation better than membranes that do not contain ibuprofen, through anti-adhesion and anti-inflammatory actions.

Modification of the crystal habit of celecoxib for improved processability.

PubMed

Banga, Sheere; Chawla, Garima; Varandani, Deepak; Mehta, B R; Bansal, Arvind K

2007-01-01

Crystallization is often used in the pharmaceutical industry for purification and isolation of drugs, and also as a means of generating polymorphs or isomorphs. The aim of this study was to investigate the role of extrinsic crystallization parameters on the crystallized product, with special emphasis on improving the mechanical properties of acicular celecoxib. Celecoxib isomorphs were prepared using different techniques (solvent crystallization and vapour diffusion) and crystallization conditions (solvents, stirring, degree of supersaturation, crystallization temperature and seeding). Powder X-ray diffractometry, spectroscopic and thermal methods were used to investigate physical characteristics of crystals. Growth kinetics and aggregation dynamics of crystallization in polar and non-polar solvents were simulated using a dynamic light scattering method. The quick appearance of broad peaks over the range of 10-8000 nm in chloroform during crystallization simulation studies indicated faster aggregation in non-polar solvents. Aspect ratio, flow, compressibility and surface area of recrystallized products were also determined. Surface topography was determined by atomic force microscopy and the lath-shaped crystals (aspect ratio of 2-4) exhibited a roughness index of 1.79 in comparison with 2.92 for needles. Overall, the lath-shaped isomorphs exhibited improved flow and better compressibility.

Ibuprofen does not affect serum electrolyte concentrations after an ultradistance run

PubMed Central

Dumke, Charles L; Nieman, David C; Oley, Kevin; Lind, Robert H

2007-01-01

Objective To determine the effects of ibuprofen on serum electrolyte concentrations after a 160 km running race. Methods Twenty nine subjects (mean (SD) age 47.9 (7.4) years) ingested 600 mg ibuprofen the day before, and 1200 mg ibuprofen during, a 160 km competitive trail running race (approximately every 4 h in 200 mg doses). Twenty five control subjects (mean (SD) age 46.8 (10.3) years) avoided ingestion of ibuprofen before or during the race. Blood was drawn on the day before the race and immediately after the race. Serum biochemical profiles were analysed by a clinical laboratory. Significant effects of treatment and time were determined with a general linear model with repeated measures. Results Subjects in the two groups did not differ by age, training volume, race experience, body mass index, body fat, or finishing time (25.8 (3.3) vs 25.6 (3.9) h). Body weight did not change significantly over the race (measured before, mid‐race (90 km), and after). Ibuprofen ingestion did not significantly affect any of the serum markers including creatine kinase (p = 0.16). A significant decrease in serum sodium (p = 0.006), potassium (p = 0.001), chloride (p<0.001), calcium (p<0.001), albumin (p<0.001) and globulin (p<0.001) was observed after the race. Increases were seen in creatine kinase (p<0.001), creatinine (p<0.001), blood urea nitrogen (p<0.001), uric acid (p<0.001) and glucose (p<0.001) as the result of the race. Conclusions These data suggest that the non‐specific cyclo‐oxygenase inhibitor, ibuprofen, does not alter serum electrolyte concentrations during ultradistance running. However, the stress of ultradistance running appears to be related to significant changes in certain serum markers. PMID:17331976

Celecoxib enhances the anti-inflammatory effects of farnesylthiosalicylic acid on T cells independent of prostaglandin E(2) production.

PubMed

Mor, Adam; Aizman, Elizabeta; Kloog, Yoel

2012-10-01

Celecoxib (Celebrex(®)), a non-steroidal anti-inflammatory drug and selective cyclooxygenase-2 inhibitor, is widely used to treat arthritis and other inflammatory disorders. Awareness of its anti-proliferative properties has prompted another indication for its use, in preventing colon polyps in high-risk populations. Farnesylthiosalicylic acid (FTS; Salirasib(®)), designed to inhibit oncogenic Ras and currently under evaluation in phase I/II and II clinical trials, was recently shown by our group to exert anti-inflammatory effects on both lymphocytes and mast cells. Here we examined whether celecoxib combined with FTS would enhance this anti-inflammatory activity. While each drug separately inhibited Ras activation in these cells, their combination yielded more marked inhibition as well as further inhibition of ERK phosphorylation, lymphocyte adhesion, and interleukin-2 secretion. The inhibitory effects, moreover, were independent of prostaglandin E(2) secretion. These data point to the promising potential of combined treatment with celecoxib and FTS for inflammatory disorders involving lymphocytes.

Ibuprofen hepatic encephalopathy, hepatomegaly, gastric lesion and gastric pentadecapeptide BPC 157 in rats.

PubMed

Ilic, Spomenko; Drmic, Domagoj; Zarkovic, Kamelija; Kolenc, Danijela; Brcic, Luka; Radic, Bozo; Djuzel, Viktor; Blagaic, Alenka Boban; Romic, Zeljko; Dzidic, Senka; Kalogjera, Livije; Seiwerth, Sven; Sikiric, Predrag

2011-09-30

Chronic ibuprofen (0.4 g/kg intraperitoneally, once daily for 4 weeks) evidenced a series of pathologies, not previously reported in ibuprofen-dosed rats, namely hepatic encephalopathy, gastric lesions, hepatomegaly, increased AST and ALT serum values with prolonged sedation/unconsciousness, and weight loss. In particular, ibuprofen toxicity was brain edema, particularly in the cerebellum, with the white matter being more affected than in gray matter. In addition, damaged and red neurons, in the absence of anti-inflammatory reaction was observed, particularly in the cerebral cortex and cerebellar nuclei, but was also present although to a lesser extent in the hippocampus, dentate nucleus and Purkinje cells. An anti-ulcer peptide shown to have no toxicity, the stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, MW 1419, 10 μg, 10 ng/kg) inhibited the pathology seen with ibuprofen (i) when given intraperitoneally, immediately after ibuprofen daily or (ii) when given in drinking water (0.16 μg, 0.16 ng/ml). Counteracted were all adverse effects, such as hepatic encephalopathy, the gastric lesions, hepatomegaly, increased liver serum values. In addition, BPC 157 treated rats showed no behavioral disturbances and maintained normal weight gain. Thus, apart from efficacy in inflammatory bowel disease and various wound treatments, BPC 157 was also effective when given after ibuprofen. Copyright © 2011 Elsevier B.V. All rights reserved.

First-dose analgesic effect of the cyclo-oxygenase-2 selective inhibitor lumiracoxib in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled comparison with celecoxib [NCT00267215

PubMed Central

Wittenberg, Ralf H; Schell, Ernest; Krehan, Gerhard; Maeumbaed, Roland; Runge, Hans; Schlüter, Peter; Fashola, Taiwo OA; Thurston, Helen J; Burger, Klaus J; Trechsel, Ulrich

2006-01-01

Cyclo-oxygenase-2 selective inhibitors are frequently used to manage osteoarthritis. We compared the analgesic efficacy of the novel cyclo-oxygenase-2 selective inhibitor lumiracoxib (Prexige®) versus placebo and celecoxib in patients with knee osteoarthritis. This seven day, double-blind, placebo and active comparator controlled, parallel group study included 364 patients aged ≥50 years with moderate-to-severe symptomatic knee osteoarthritis. Patients received lumiracoxib 400 mg/day (four times the recommended chronic dose in osteoarthritis; n = 144), placebo (n = 75), or celecoxib 200 mg twice daily (n = 145). The primary variable was actual pain intensity difference (100 mm visual–analogue scale) between baseline and the mean of three hour and five hour assessments after the first dose. Actual pain intensity difference, average and worst pain, pain relief and functional status (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC™]) were measured over seven days. Patients also completed a global evaluation of treatment effect at study end or premature discontinuation. For the primary variable, the superiority of lumiracoxib versus placebo, the noninferiority of lumiracoxib versus celecoxib, and the superiority of lumiracoxib versus celecoxib were assessed by closed test procedure adjusting for multiplicity, thereby maintaining the overall 5% significance level. In addition, celecoxib was assessed versus placebo in a predefined exploratory manner to assess trial sensitivity. Lumiracoxib provided better analgesia than placebo 3–5 hours after the first dose (P = 0.004) through to study end. The estimated difference between lumiracoxib and celecoxib 3–5 hours after the first dose was not significant (P = 0.185). Celecoxib was not significantly different from placebo in this analysis (P = 0.069). At study end 13.9% of lumiracoxib-treated patients reported complete pain relief versus 5.5% and 5.3% of celecoxib and placebo recipients

Microbial Removal of the Pharmaceutical Compounds Ibuprofen and Diclofenac from Wastewater

PubMed Central

Inderfurth, Nadia; Schraa, Gosse; Kujawa-Roeleveld, Katarzyna; Rijnaarts, Huub

2013-01-01

Studies on the occurrence of pharmaceuticals show that the widely used pharmaceuticals ibuprofen and diclofenac are present in relevant concentrations in the environment. A pilot plant treating hospital wastewater with relevant concentrations of these pharmaceuticals was evaluated for its performance to reduce the concentration of the pharmaceuticals. Ibuprofen was completely removed, whereas diclofenac yielded a residual concentration, showing the necessity of posttreatment to remove diclofenac, for example, activated carbon. Successively, detailed laboratory experiments with activated sludge from the same wastewater treatment plant showed bioremediation potential in the treatment plant. The biological degradation pathway was studied and showed a mineralisation of ibuprofen and degradation of diclofenac. The present microbes were further studied in laboratory experiments, and DGGE analyses showed the enrichment and isolation of highly purified cultures that degraded either ibuprofen or diclofenac. This research illuminates the importance of the involved bacteria for the effectiveness of the removal of pharmaceuticals in a wastewater treatment plant. A complete removal of pharmaceuticals from wastewater will stimulate water reuse, addressing the worldwide increasing demand for clean and safe fresh water. PMID:24350260

Single dose oral ibuprofen plus caffeine for acute postoperative pain in adults.

PubMed

Derry, Sheena; Wiffen, Philip J; Moore, R Andrew

2015-07-14

There is good evidence that combining two different analgesics in fixed doses in a single tablet can provide better pain relief in acute pain and headache than either drug alone, and that the drug-specific benefits are essentially additive. This appears to be broadly true in postoperative pain and migraine headache across a range of different drug combinations, and when tested in the same and different trials. Adding caffeine to analgesics also increases the number of people obtaining good pain relief. Combinations of ibuprofen and caffeine are available without prescription in some parts of the world. To assess the analgesic efficacy and adverse effects of a single oral dose of ibuprofen plus caffeine for moderate to severe postoperative pain, using methods that permit comparison with other analgesics evaluated in standardised trials using almost identical methods and outcomes. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Oxford Pain Relief Database, two clinical trial registries, and the reference lists of articles. The date of the most recent search was 1 February 2015. Randomised, double-blind, placebo- or active-controlled clinical trials of single dose oral ibuprofen plus caffeine for acute postoperative pain in adults. Two review authors independently considered trials for inclusion in the review, assessed risk of bias, and extracted data. We used the area under the pain relief versus time curve to derive the proportion of participants with at least 50% pain relief over six hours prescribed either ibuprofen plus caffeine or placebo. We calculated the risk ratio (RR) and number needed to treat to benefit (NNT). We used information on the use of rescue medication to calculate the proportion of participants requiring rescue medication and the weighted mean of the median time to use. We also collected information on adverse effects. We identified five randomised, double-blind studies with 1501 participants, but

Effects of acetaminophen and ibuprofen in children with migraine receiving preventive treatment with magnesium.

PubMed

Gallelli, Luca; Avenoso, Tiziana; Falcone, Daniela; Palleria, Caterina; Peltrone, Francesco; Esposito, Maria; De Sarro, Giovambattista; Carotenuto, Marco; Guidetti, Vincenzo

2014-02-01

The purpose of this study was to evaluate both the effects of ibuprofen and/or acetaminophen for the acute treatment of primary migraine in children in or out prophylactic treatment with magnesium. Children ranging from the ages of 5 to 16 years with at least 4 attack/month of primary migraine were eligible for participation the study. A visual analog scale was used to evaluate pain intensity at the moment of admission to the study (start of the study) and every month up to 18 months later (end of the study). One hundred sixty children of both sexes aged 5-16 years were enrolled and assigned in 4 groups to receive a treatment with acetaminophen or ibuprofen without or with magnesium. Migraine pain endurance and monthly frequency were similar in the 4 groups. Both acetaminophen and ibuprofen induced a significant decrease in pain intensity (P < .01), without a time-dependent correlation, but did not modify its frequency. Magnesium pretreatment induced a significant decrease in pain intensity (P < .01) without a time-dependent correlation in both acetaminophen- and ibuprofen-treated children and also significantly reduced (P < .01) the pain relief timing during acetaminophen but not during ibuprofen treatment (P < .01). In both acetaminophen and ibuprofen groups, magnesium pretreatment significantly reduced the pain frequency (P < .01). Magnesium increased the efficacy of ibuprofen and acetaminophen with not age-related effects. © 2013 American Headache Society.

Combination of a poxvirus-based vaccine with a cyclooxygenase-2 inhibitor (celecoxib) elicits antitumor immunity and long-term survival in CEA.Tg/MIN mice.

PubMed

Zeytin, Hasan E; Patel, Arti C; Rogers, Connie J; Canter, Daniel; Hursting, Stephen D; Schlom, Jeffrey; Greiner, John W

2004-05-15

The present study was designed to determine whether: (a) chronic administration of dietary celecoxib (Celebrex), a potent nonsteroidal anti-inflammatory drug, which targets the cyclooxygenase-2 (COX-2) enzyme, negatively impacts host immunity; and (b) celecoxib can be coupled with a poxvirus-based vaccine to impact tumor burden in a murine tumor model of spontaneous adenomatous polyposis coli. Naive mice fed the celecoxib-supplemented diets developed eosinophilia with lowered plasma prostaglandin E(2) levels and reduced COX-2 mRNA expression levels in their splenic T cells. Responses of splenic T, B, and natural killer cells to broad-based and antigen-specific stimuli were, for the most part, unchanged in those mice as well as COX-2 knockout mice; exceptions included: (a) reduced IFN-gamma production by concanavalin A- or antigen-stimulated T cells; and (b) heightened lipopolysaccharide response of naive B cells from mice fed a diet supplemented with 1000 ppm of celecoxib. When transgenic mice that express the human carcinoembryonic antigen (CEA) gene (CEA transgenic) were bred with mice bearing a mutation in the Apc(Delta850) gene (multiple intestinal neoplasia mice), the progeny (CEA transgenic/multiple intestinal neoplasia) spontaneously develop multiple intestinal neoplasms that overexpress CEA and COX-2. Beginning at 30 days of age, the administration of a diversified prime/boost recombinant CEA-poxvirus-based vaccine regimen or celecoxib (1000 ppm)-supplemented diet reduced the number of intestinal neoplasms by 54% and 65%, respectively. Combining the CEA-based vaccine with the celecoxib-supplemented diet reduced tumor burden by 95% and significantly improved overall long-term survival. Both tumor reduction and improved overall survival were achieved without any evidence of autoimmunity directed at CEA-expressing or other normal tissues. Celecoxib is prescribed for the treatment of familial adenomatous polyposis in humans, and the CEA-based vaccines have been

Effect of celecoxib plus standard chemotherapy on serum levels of vascular endothelial growth factor and cyclooxygenase-2 in patients with gastric cancer.

PubMed

Han, Xiaopeng; Li, Hongtao; Su, Lin; Zhu, Wankun; Xu, Wei; Li, Kun; Zhao, Qingchuan; Yang, Hua; Liu, Hongbin

2014-03-01

Elevated serum levels of vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) are associated with poor prognosis in patients with gastric cancer. Little is known regarding the clinical benefits of combining celecoxib, a selective inhibitor of COX-2, with standard chemotherapy regimens for the treatment of gastric cancer patients. In this study, we investigated the effect of the combinatorial use of celecoxib with standard chemotherapy on the serum levels of VEGF and COX-2 in patients with gastric cancer. In our study, 80 patients with gastric cancer who underwent laparoscopic radical surgery were randomized into two groups, the combination [celecoxib plus standard oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX4) chemotherapy, n=40] and the FOLFOX4 alone (n=40) groups. In the combination group, celecoxib was orally administered to the patients (400 mg, twice daily). The serum levels of VEGF and COX-2 were measured by ELISA prior to and following surgery. We detected no significant difference in the serum levels of VEGF and COX-2 between the combination and FOLFOX4 alone groups prior to chemotherapy (P>0.05). However, after 6 cycles of chemotherapy, there was a greater decrease in the serum levels of VEGF and COX-2 in the combination group compared to those in the FOLFOX4 group (P<0.01). In addition, the serum levels of VEGF and COX-2 were closely correlated in patients with gastric adenocarcinoma prior to treatment. Our data indicated that, when combined with standard chemotherapy, celecoxib may reduce the serum levels of VEGF and COX-2, suggesting that COX-2 inhibitors may be of therapeutic value through the inhibition of tumor angiogenesis and the prevention of recurrence or metastasis. Thus, celecoxib may be a useful adjuvant agent to standard chemotherapy in patients with advanced gastric cancer.

Antiproliferative effect of a novel nitro-oxy derivative of celecoxib in human colon cancer cells: role of COX-2 and nitric oxide.

PubMed

Bocca, Claudia; Bozzo, Francesca; Bassignana, Andrea; Miglietta, Antonella

2010-07-01

It has been shown previously that a novel nitrooxy derivative of celecoxib exerts antiproliferative and pro-apoptotic effects in human colon cancer cells. The aim of this study was to elucidate whether these biological properties depend on COX-2 inhibition and/or NO release. Therefore, the derivative was decomposed into the parent compound celecoxib and the NO donor benzyl nitrate and the biological role of each was tested in COX-2-positive (HT-29) and -negative (SW-480) colon cancer cells. The main findings were that the nitro-oxy derivative behaved like celecoxib in HT-29 cells in terms of COX-2 and ERK/MAPK inhibition, as well as induction of apoptosis, while the benzyl nitrate had no such effects. Interestingly, the beta-catenin system was activated by the nitro-oxy derivative as well as by benzyl nitrate alone more potently than by the parent compound celecoxib, suggesting a possible regulatory role for NO. In SW480 cells, these activities were substantially less pronounced, suggesting the presence of COX-2-dependent mechanisms in the modulation of these parameters.

Chemoprevention of Nonmelanoma Skin Cancer With Celecoxib: A Randomized, Double-Blind, Placebo-Controlled Trial

PubMed Central

Viner, Jaye L.; Pentland, Alice P.; Cantrell, Wendy; Bailey, Howard; Kang, Sewon; Linden, Kenneth G.; Heffernan, Michael; Duvic, Madeleine; Richmond, Ellen; Elewski, Boni E.; Umar, Asad; Bell, Walter; Gordon, Gary B.

2010-01-01

Background Preclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib, a cyclooxygenase 2 inhibitor, as a chemopreventive agent for actinic keratoses, the premalignant precursor of nonmelanoma skin cancers, and for nonmelanoma skin cancers, including cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs). Methods A double-blind placebo-controlled randomized trial involving 240 subjects aged 37–87 years with 10–40 actinic keratoses was conducted at eight US academic medical centers. Patients were randomly assigned to receive 200 mg of celecoxib or placebo administered orally twice daily for 9 months. Subjects were evaluated at 3, 6, 9 (ie, completion of treatment), and 11 months after randomization. The primary endpoint was the number of new actinic keratoses at the 9-month visit as a percentage of the number at the time of randomization. In an intent-to-treat analysis, the incidence of actinic keratoses was compared between the two groups using t tests. In exploratory analyses, we evaluated the number of nonmelanoma skin cancers combined and SCCs and BCCs separately per patient at 11 months after randomization using Poisson regression, after adjustment for patient characteristics and time on study. The numbers of adverse events in the two treatment arms were compared using χ2 or Fisher exact tests. All statistical tests were two-sided. Results There was no difference in the incidence of actinic keratoses between the two groups at 9 months after randomization. However, at 11 months after randomization, there were fewer nonmelanoma skin cancers in the celecoxib arm than in the placebo arm (mean cumulative tumor number per patient 0.14 vs 0.35; rate ratio [RR] = .43, 95% confidence interval [CI] = 0.24 to 0.75; P = .003). After adjusting for age, sex, Fitzpatrick skin type, history of actinic keratosis at randomization, nonmelanoma

Gastroprotective effects of several H2RAs on ibuprofen-induced gastric ulcer in rats.

PubMed

Liu, Jing; Sun, Dan; He, Jinfeng; Yang, Chengli; Hu, Tingting; Zhang, Lijing; Cao, Hua; Tong, Ai-Ping; Song, Xiangrong; Xie, Yongmei; He, Gu; Guo, Gang; Luo, Youfu; Cheng, Ping; Zheng, Yu

2016-03-15

Ibuprofen is the first line of treatment for osteoarthritis and arthritis. The main side effects of ibuprofen especially in long-term treatment include gastric ulcer, duodenal ulcer and indigestion etc. Therefore, screening drugs with effective gastric protective effects and low toxicity for combination therapy with ibuprofen is necessary. The mechanism of gastric damage induced by ibuprofen is still unclear, however, cell damage caused by reactive oxygen species (ROS) is considered as the main reason. Preliminary screening of literature with the criteria of low toxicity led to four histamine-2 receptor antagonists (H2RAs): nizatidine, famotidine, lafutidine, and roxatidine acetate, which were selected for further investigation. These drugs were evaluated systemically by examining the gastric ulcer index, lipid peroxidation (LPO), membrane permeability, toxicity to main organs, and the influence on the activity of antioxidant enzymes, and myeloperoxidase (MPO). Nizatidine was found to be the best gastric protective agent. It exhibited excellent protective effect by increasing antioxidant enzyme activity, decreasing MPO activity, reducing LPO, and membrane permeability. Combination treatment with nizatidine and ibuprofen did not show any significant toxicity. Nizatidine was considered as a good option for combination therapy with ibuprofen especially for diseases that require long-term treatment such as arthritis and osteoarthritis. Copyright © 2016 Elsevier Inc. All rights reserved.

Synergistic anticancer effects of combined γ-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFκB signaling

PubMed Central

Shirode, Amit B.; Sylvester, Paul W.

2009-01-01

The selective cyclooxygenase (COX)-2 inhibitor, celecoxib, and the vitamin E isoform, γ-tocotrienol, both display potent anticancer activity. However, high dose clinical use of selective COX-2 inhibitors has been limited by gastrointestinal and cardiovascular toxicity, whereas limited absorption and transport of γ-tocotrienol by the body has made it difficult to obtain and sustain therapeutic levels in the blood and target tissues. Studies were conducted to characterize the synergistic anticancer antiproliferative effects of combined low dose celecoxib and γ-tocotrienol treatment on mammary tumor cells in culture. The highly malignant mouse +SA mammary epithelial cells were maintained in culture on serum-free defined control or treatment media. Treatment effects on COX-1, COX-2, Akt, NFκB and prostaglandin E2 (PGE2) synthesis was assessed following a 3- or 4-day culture period. Treatment with 3–4 μM γ-tocotrienol or 7.5–10 μM celecoxib alone significantly inhibited +SA cell growth in a dose-responsive manner. However, combined treatment with subeffective doses of γ-tocotrienol (0.25 μM) and celecoxib (2.5 μM) resulted in a synergistic antiproliferative effect, as determined by isobologram analysis, and this growth inhibitor effect was associated with a reduction in PGE2 synthesis, and decrease in COX-2, phospho-Akt (active), and phospho-NFκB (active) levels. These results demonstrate that the synergistic anticancer effects of combined celecoxib and γ-tocotrienol therapy are mediated by COX-2 dependent and independent mechanisms. These findings also suggest that combination therapy with these agents may provide enhanced therapeutic response in breast cancer patients, while avoiding the toxicity associated with high-dose COX-2 inhibitor monotherapy. PMID:19954924

Effectiveness and safety of Glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of osteoarthritis of the knee

PubMed Central

Zeng, Chao; Wei, Jie; Li, Hui; Wang, Yi-lun; Xie, Dong-xing; Yang, Tuo; Gao, Shu-guang; Li, Yu-sheng; Luo, Wei; Lei, Guang-hua

2015-01-01

This study aimed to investigate the effectiveness and safety of glucosamine, chondroitin, the two in combination, or celecoxib in the treatment of knee osteoarthritis (OA). PubMed, Embase and Cochrane Library were searched through from inception to February 2015. A total of 54 studies covering 16427 patients were included. Glucosamine plus chondroitin, glucosamine alone, and celecoxib were all more effective than placebo in pain relief and function improvement. Specifically, celecoxib is most likely to be the best treatment option, followed by the combination group. All treatment options showed clinically significant improvement from baseline pain, but only glucosamine plus chondroitin showed clinically significant improvement from baseline function. In terms of the structure-modifying effect, both glucosamine alone and chondroitin alone achieved a statistically significant reduction in joint space narrowing. Although no significant difference was observed among the five options with respect to the three major adverse effects (withdrawal due to adverse events, serious adverse events and the number of patients with adverse events), the additional classical meta-analysis showed that celecoxib exhibited a higher rate of gastrointestinal adverse effect comparing with the placebo group. The present study provided evidence for the symptomatic efficacy of glucosamine plus chondroitin in the treatment of knee OA. PMID:26576862

[Characterization of microstructure of ibuprofen-hydroxypropyl-beta-cyclodextrin and ibuprofen-beta-cyclodextrin by atomic force microscope].

PubMed

Wang, Li-juan; Zhu, Zhao-jing; Che, Ke-ke; Ju, Feng-ge

2008-09-01

The microstructures of ibuprofen-hydroxypropyl-bets-cyclodextrin (IBU-HP-beta-CyD) and ibuprofen-beta-cyclodextrin (IBU-beta-CyD) were observed by atomic force microscope (AFM). The high resolving capability of AFM has the tungsten filament probe with the spring constant of 0.06 N x m(-1). Samples were observed in a small scale scanning area of 10.5 nm x 10.5 nm and 800 x 800 pixels. The original scanning images were gained by tapping mode at room temperature. Their three-dimensional reconstruction of microstructure was performed by G3DR software. The outer diameters of HP-beta-CyD and beta-CyD are 1.53 nm. The benzene diameter of IBU is 0.62 nm, fitting to the inner diameters of HP-beta-CyD and beta-CyD. The benzene and hydrophobic chain of IBU enter into the hole of cyclodextrin at 1:1 ratio. The results were evidenced by IR, X-ray diffraction and the phase solubility.

Characteristics and clinical implications of the pharmacokinetic profile of ibuprofen in patients with knee osteoarthritis.

PubMed

Gallelli, L; Galasso, O; Urzino, A; Saccà, S; Falcone, D; Palleria, C; Longo, P; Corigliano, A; Terracciano, R; Savino, R; Gasparini, G; De Sarro, G; Southworth, S R

2012-12-01

Ibuprofen is a non-selective cyclo-oxygenase (COX)-1/COX-2 inhibitor used to treat pain conditions and inflammation. Limited data have been published concerning the pharmacokinetic profile and clinical effects of ibuprofen in patients with osteoarthritis (OA). In this paper we compared the pharmacokinetic and clinical profile of ibuprofen (at a dosage of from 800 mg/day to 1800 mg/day) administered in patients affected by severe knee OA. Ibuprofen was administered for 7 days to patients who were scheduled to undergo knee arthroplasty due to OA. After 7 days, the ibuprofen concentration in plasma and synovial fluid was measured through both high-performance liquid chromatography (HPLC)-UV and gas chromatography-mass spectroscopy (GC/MS), while clinical effects were evaluated through both visual analogue scale (VAS) and Western Ontario and McMaster Universities (WOMAC) scores. The Naranjo scale and the WHO causality assessment scale were used for estimating the probability of adverse drug reactions (ADRs). The severity of ADRs was assessed by the modified Hartwig and Siegel scale. Ibuprofen showed a dose-dependent diffusion in both plasma and synovial fluid, which was related to the reduction of pain intensity and improvement of health status, without the development of ADRs. Ibuprofen at higher dosages can be expected to provide better control of OA symptoms as a result of higher tissue distribution.

Efficacy and safety of rectal ibuprofen for patent ductus arteriosus closure in very low birth weight preterm infants.

PubMed

Demir, Nihat; Peker, Erdal; Ece, İbrahim; Balahoroğlu, Ragıp; Tuncer, Oğuz

2017-09-01

To compare rectal ibuprofen with oral ibuprofen for the closure of hemodynamically significant patent ductus arteriosus (hsPDA) in very low birth weight (VLBW) preterm infants. In a prospective, randomized study, 72 VLBW infants who had hsPDA received either rectal or oral ibuprofen. The plasma concentration of ibuprofen and renal functions were determined in both groups by the high-performance liquid chromatography (HPLC) method and cystatin-C (cys-C), respectively. The hsPDA closure rate of the group that received rectal ibuprofen was similar to oral ibuprofen (86.1% versus 83.3%) after the first course of the treatment (p = 0.745). A statistically significant difference was identified between the mean plasma cys-C levels before and after treatment in both the rectal and oral ibuprofen groups (p = 0.004 and p< 0.001, respectively). The mean plasma ibuprofen concentration was similar in both groups after the first dose (rectal 44.06 ± 12.4; oral, 48.28 ± 22.8) and the third dose (rectal, 45.34 ± 24.3; oral, 48.94 ± 24.8) (p > 0.05 for all values). Rectal ibuprofen is as effective as oral ibuprofen for hsPDA closure in VLBW infants. The rise in the cys-C level with rectal and oral treatment shows that patients with borderline renal function should be evaluated and followed closely.

An examination of the thermodynamics of fusion, vaporization, and sublimation of ibuprofen and naproxen by correlation gas chromatography.

PubMed

Maxwell, Rachel; Chickos, James

2012-02-01

The vaporization enthalpies of (S)-ibuprofen and (S)-naproxen measured by correlation gas chromatography at T = 298.15 K are reported and compared with literature values. Adjustment of the fusion enthalpies of (RS)- and (S)-ibuprofen and (S)-naproxen to T = 298.15 K and combined with the vaporization enthalpy of the (S)-enantiomer of both ibuprofen and naproxen also at T = 298.15 K resulted in the sublimation enthalpies of both (S)-enantiomers. On the assumption that the vaporization enthalpy of the racemic form of ibuprofen is within the experimental uncertainty of the chiral form, the sublimation enthalpy of racemic ibuprofen was also evaluated. The vaporization and sublimation enthalpies compare favorably to the most of the literature values for the racemic form of ibuprofen but differ from the value reported for chiral ibuprofen. The literature values of (S)-naproxen are somewhat smaller than the values measured in this work. The following vaporization enthalpies were measured for (S)-ibuprofen and (S)-naproxen, respectively: ΔH(vap) (298.15 K), 106.0 ± 5.5, 132.2 ± 5.0 kJ·mol(-1) . Sublimation enthalpies of 122.7 ± 5.6 and 155.2 ± 7.1 kJ·mol(-1) were calculated for the (S)-enantiomers of ibuprofen and naproxen and a value of 128.9 ± 5.8 kJ·mol(-1) was estimated for the racemic form of ibuprofen. Copyright © 2011 Wiley Periodicals, Inc.

Acetaminophen versus Ibuprofen in Young Children with Mild Persistent Asthma.

PubMed

Sheehan, William J; Mauger, David T; Paul, Ian M; Moy, James N; Boehmer, Susan J; Szefler, Stanley J; Fitzpatrick, Anne M; Jackson, Daniel J; Bacharier, Leonard B; Cabana, Michael D; Covar, Ronina; Holguin, Fernando; Lemanske, Robert F; Martinez, Fernando D; Pongracic, Jacqueline A; Beigelman, Avraham; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Chmiel, James F; Daines, Cori L; Daines, Michael O; Gaffin, Jonathan M; Gentile, Deborah A; Gower, W Adam; Israel, Elliot; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Ly, Ngoc; Marbin, Jyothi; Morgan, Wayne J; Myers, Ross E; Olin, J Tod; Peters, Stephen P; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Thyne, Shannon M; Wechsler, Michael E; Phipatanakul, Wanda

2016-08-18

Studies have suggested an association between frequent acetaminophen use and asthma-related complications among children, leading some physicians to recommend that acetaminophen be avoided in children with asthma; however, appropriately designed trials evaluating this association in children are lacking. In a multicenter, prospective, randomized, double-blind, parallel-group trial, we enrolled 300 children (age range, 12 to 59 months) with mild persistent asthma and assigned them to receive either acetaminophen or ibuprofen when needed for the alleviation of fever or pain over the course of 48 weeks. The primary outcome was the number of asthma exacerbations that led to treatment with systemic glucocorticoids. Children in both groups received standardized asthma-controller therapies that were used in a simultaneous, factorially linked trial. Participants received a median of 5.5 doses (interquartile range, 1.0 to 15.0) of trial medication; there was no significant between-group difference in the median number of doses received (P=0.47). The number of asthma exacerbations did not differ significantly between the two groups, with a mean of 0.81 per participant with acetaminophen and 0.87 per participant with ibuprofen over 46 weeks of follow-up (relative rate of asthma exacerbations in the acetaminophen group vs. the ibuprofen group, 0.94; 95% confidence interval, 0.69 to 1.28; P=0.67). In the acetaminophen group, 49% of participants had at least one asthma exacerbation and 21% had at least two, as compared with 47% and 24%, respectively, in the ibuprofen group. Similarly, no significant differences were detected between acetaminophen and ibuprofen with respect to the percentage of asthma-control days (85.8% and 86.8%, respectively; P=0.50), use of an albuterol rescue inhaler (2.8 and 3.0 inhalations per week, respectively; P=0.69), unscheduled health care utilization for asthma (0.75 and 0.76 episodes per participant, respectively; P=0.94), or adverse events. Among

Using milk fat to reduce the irritation and bitter taste of ibuprofen

PubMed Central

Bennett, Samantha M.; Zhou, Lisa; Hayes, John E.

2012-01-01

Bitterness and irritation elicited by pharmaceutically active molecules remain problematic for pediatric medications, fortified foods and dietary supplements. Few effective methods exist for reducing these unpalatable sensations, negatively impacting medication compliance and intake of beneficial phytonutrients. A physicochemical approach to masking these sensations may be the most successful approach for generalizability to a wide range of structurally and functionally unique compounds. Here, solutions of the non-steroidal anti- inflammatory drug, ibuprofen, were prepared in milk products with varying fat content. Our hypothesis, based on other reports of similar phenomena, was that increasing the fat content would cause ibuprofen to selectively partition into the fat phase, thereby reducing interaction with sensory receptors and decreasing adversive sensations. Quantification of the aqueous concentration of ibuprofen was performed using an isocratic HPLC method coupled with an external standard curve. Sensory testing showed a modest but significant decrease (~20%) in irritation ratings between the skim milk (0% fat) and the half-and-half (11% fat) samples, indicating that increased fat may contribute to a reduced sensory response. Bitterness was not reduced, remaining constant over all fat levels. The HPLC results indicate a constant amount of ibuprofen remained in the aqueous phase regardless of fat level, so a simple partitioning hypothesis cannot explain the reduced irritancy ratings. Association of ionized ibuprofen with continuous phase solutes such as unabsorbed protein should be explored in future work. PMID:23527314

Celecoxib Ameliorates Non-Alcoholic Steatohepatitis in Type 2 Diabetic Rats via Suppression of the Non-Canonical Wnt Signaling Pathway Expression

PubMed Central

Tian, Feng; Zhang, Ya Jie; Li, Yu; Xie, Ying

2014-01-01

Our aim was to test whether pharmacological inhibition of cycloxygenase-2 (COX-2) reverses non-alcoholic steatohepatitis (NASH) in type 2 diabetes mellitus (T2DM) rats via suppression of the non-canonical Wnt signaling pathway expression. Twenty-four male Sprague-Dawley rats were randomly distributed to two groups and were fed with a high fat and sucrose (HF-HS) diet or a normal chow diet, respectively. After four weeks, rats fed with a HF-HS diet were made diabetic with low-dose streptozotocin. At the 9th week the diabetic rats fed with a HF-HS diet or the non-diabetic rats fed with a normal chow diet were further divided into two subgroups treated with vehicle or celecoxib (a selective COX-2 inhibitor, 10 mg/Kg/day, gavage) for the last 4 weeks, respectively. At the end of the 12th week, rats were anesthetized. NASH was assessed by histology. Related cytokine expression was measured at both the protein and gene levels through immunohistochemistry (IHC), Western blot and real-time PCR. T2DM rats fed with a HF-HS diet developed steatohepatitis and insulin resistance associated with elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), insulin levels and the non-alcoholic fatty liver disease (NAFLD) activity score (NAS). The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 were all significantly increased in the T2DM-NASH group compared with the control and control-cele group. Hepatic injury was improved by celecoxib in T2DM-NASH-Cele group indicated by reduced serum ALT and AST levels and hepatic inflammation was reduced by celecoxib showed by histology and the NAFLD activity score (NAS). Serum related metabolic parameters, HOMA-IR and insulin sensitivity index were all improved by celecoxib. The expression of Wnt5a, JNK1, NF-κB p65, and COX-2 expression were all suppressed by celecoxib in T2DM-NASH-Cele group. The results of the present study indicated that celecoxib ameliorated NASH in T2DM rats via suppression of the non-canonical Wnt

New microbes as causative agents of Ibuprofen degradation capabilities in the hyporheic zone of a lowland stream

NASA Astrophysics Data System (ADS)

Njeru, Cyrus; Posselt, Malte; Horn, Marcus A.

2017-04-01

Ibuprofen is a non-steroidal anti-inflammatory pain reliever and among pharmaceutical residues detected in aquatic environments. Widespread use of the drug and incomplete removal during waste water treatment results in its persistence in effluents and receiving waters. Potential total removal by microbial activity in the hyporheic zone (HZ) of rivers downstream of wastewater treatment plant discharge sites has been hypothesized. Ibuprofen degradation associated microbial communities in are essentially unknown. To address this hypothesis, two sets of oxic HZ sediment microcosms spiked with ibuprofen only (5, 40, 200 and 400 µM), or ibuprofen and 1 mM acetate were set up under laboratory conditions. Ibuprofen degradation in non-sterile relative to autoclaved sediments indicated removal by microbial degradation. Ibuprofen was completely consumed in the absence and presence of supplemental acetate after approximately 11 and 16 days, respectively. Refeeding of ibuprofen and acetate after the first depletion resulted in complete degradation within 24 hours in all treatments. Metabolites of ibuprofen included 1-, 2-, 3-hydroxy- and carboxyibuprofen. Quantitative real-time PCR revealed no pronounced differences in copy numbers of 16S rRNA gene or transcripts between non-spiked controls and treatments. Time resolved triplicate amplicon Illumina MiSeq sequencing targeting the 16S rRNA genes and transcripts revealed increased relative abundances of Proteobacteria, Acidobacteria, Actinobacteria and Firmicutes in treatments with compared to those without ibuprofen. Alpha-, Beta- and Deltaproteobacteria were most active as indicated by RNA based analyses. Enrichment and isolation yielded new Alphaproteobacteria utilizing ibuprofen as sole carbon and energy source. The collective results indicated that (i) HZ sediments sustain efficient biotic (micro-)pollutant removal and (ii) are a reservoir of hitherto unknown microbial diversity associated with such ecosystem services

IBUPROFEN DOES NOT INCREASE BLEEDING RISK IN PLASTIC SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS

PubMed Central

Kelley, Brian P.; Bennett, Katelyn G.; Chung, Kevin C.; Kozlow, Jeffrey H.

2016-01-01

Background Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen are common medications with multiple useful effects including pain relief and reduction of inflammation. However, surgeons commonly hold all NSAIDs peri-operatively because of bleeding concerns. However, not all NSAIDs irreversibly block platelet function. We hypothesized that the use of ibuprofen would have no effect on postoperative bleeding in plastic surgery patients. Methods A literature review was performed using Medline (PubMed), EMBASE, and the Cochrane Collaboration Library for primary research articles on ibuprofen and bleeding. Inclusion criteria were primary journal articles examining treatment of acute postoperative based on any modality. Data related to pain assessment, postoperative recovery, and complications were extracted. Bias assessment and meta-analysis were performed. Results A total of 881 publications were reviewed. Four primary randomized controlled trials were selected for full analysis. Articles were of high quality by bias assessment. No significant difference was noted regarding bleeding events (p = 0.32) and pain control was noted to be equivalent. Conclusion Ibuprofen is a useful medication in the setting of surgery with multiple beneficial effects. This meta-analysis represents a small set of high quality studies that suggests ibuprofen provides equivalent pain control to narcotics. Importantly, ibuprofen was not associated with an increased risk of bleeding. Further large studies will be necessary to elucidate this issue further, but ibuprofen is a safe postoperative analgesic in patients undergoing common plastic surgery soft tissue procedures. PMID:27018685

Synergistic anticancer effects of combined gamma-tocotrienol and celecoxib treatment are associated with suppression in Akt and NFkappaB signaling.

PubMed

Shirode, Amit B; Sylvester, Paul W

2010-05-01

The selective cyclooxygenase (COX)-2 inhibitor, celecoxib, and the vitamin E isoform, gamma-tocotrienol, both display potent anticancer activity. However, high dose clinical use of selective COX-2 inhibitors has been limited by gastrointestinal and cardiovascular toxicity, whereas limited absorption and transport of gamma-tocotrienol by the body has made it difficult to obtain and sustain therapeutic levels in the blood and target tissues. Studies were conducted to characterize the synergistic anticancer antiproliferative effects of combined low dose celecoxib and gamma-tocotrienol treatment on mammary tumor cells in culture. The highly malignant mouse +SA mammary epithelial cells were maintained in culture on serum-free defined control or treatment media. Treatment effects on COX-1, COX-2, Akt, NFkappaB and prostaglandin E(2) (PGE(2)) synthesis were assessed following a 3- or 4-day culture period. Treatment with 3-4 microM gamma-tocotrienol or 7.5-10 microM celecoxib alone significantly inhibited +SA cell growth in a dose-responsive manner. However, combined treatment with subeffective doses of gamma-tocotrienol (0.25 microM) and celecoxib (2.5 microM) resulted in a synergistic antiproliferative effect, as determined by isobologram analysis, and this growth inhibitory effect was associated with a reduction in PGE(2) synthesis, and decrease in COX-2, phospho-Akt (active), and phospho-NFkappaB (active) levels. These results demonstrate that the synergistic anticancer effects of combined celecoxib and gamma-tocotrienol therapy are mediated by COX-2 dependent and independent mechanisms. These findings also suggest that combination therapy with these agents may provide enhanced therapeutic response in breast cancer patients, while avoiding the toxicity associated with high-dose COX-2 inhibitor monotherapy. 2009 Elsevier Masson SAS. All rights reserved.

New Approaches for Prostate Cancer Combination Therapy

DTIC Science & Technology

2007-04-01

in DU145 cells. Strong inducers of apoptosis included Sulindac sulfide, Finasteride , Diclofenac, Flufenamic acid, Flurbiprofen, Sulindac sulfone and... Finasteride , a selective 5-alpha-reductase inhibitor, is not known to inhibit COX-2, strongly induces MDA-7/IL-24 expression and apoptosis, whereas the...ibuprofen, aspirin, acet- aminophen, and naproxen were obtained from Sigma-Aldrich (St. Louis, MO). Meloxicam, celecoxib, diclofenac, finasteride , and

Enantioselective analysis of ibuprofen in human plasma by anionic cyclodextrin-modified electrokinetic chromatography.

PubMed

Jabor, Valquíria A P; Lanchote, Vera L; Bonato, Pierina S

2002-09-01

This paper reports the development of a rapid method for the enantioselective analysis of the nonsteroidal anti-inflammatory drug ibuprofen in human plasma by capillary electrophoresis employing the anionic cyclodextrin-modified electrokinetic chromatography mode. Sample cleanup was carried out by acidification with HCl followed by liquid-liquid extraction with hexane:isopropanol (99:1 v/v). The complete enantioselective analysis was performed within 10 min, using 100 mmol L(-1) phosphoric acid/triethanolamine buffer, pH 2.6, containing 2.0% w/v sulfated beta-cyclodextrin as chiral selector; fenoprofen, another nonsteroidal anti-inflammatory drug, was used as internal standard. The calibration curves were linear over the concentration range of 0.25-125.0 microg mL(-1) for each enantiomer of ibuprofen. The mean recoveries for ibuprofen enantiomers were up to 85%. The enantiomers studied could be quantified at three different concentrations (0.5, 5.0 and 50.0 microg mL(-1)) with a coefficient of variation and relative error not higher than 15%. The quantitation limit was 0.2 microg mL(-1) for (+)-(S)- and (-)-(R)-ibuprofen using 1 mL of human plasma. The plasma endogenous compounds and other drugs did not interfere with the present assay. The analysis of real plasma samples obtained from a healthy volunteer after administration of 600 mg of racemic ibuprofen showed a maximum plasma level of 29.6 and 39.9 microg mL(-1) of (-)-(R)- and (+)-(S)-ibuprofen, respectively, and the area under plasma concentration-time curve AUC(0-infinity) (+)-(S)/AUC(0-infinity) (-)-(R) ratio was 1.87.

Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism.

PubMed

Kristensen, David Møbjerg; Desdoits-Lethimonier, Christèle; Mackey, Abigail L; Dalgaard, Marlene Danner; De Masi, Federico; Munkbøl, Cecilie Hurup; Styrishave, Bjarne; Antignac, Jean-Philippe; Le Bizec, Bruno; Platel, Christian; Hay-Schmidt, Anders; Jensen, Tina Kold; Lesné, Laurianne; Mazaud-Guittot, Séverine; Kristiansen, Karsten; Brunak, Søren; Kjaer, Michael; Juul, Anders; Jégou, Bernard

2018-01-23

Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism. Copyright © 2018 the Author(s). Published by PNAS.

Comparison of the anti-proliferation and apoptosis-induction activities of sulindac, celecoxib, curcumin, and nifedipine in mismatch repair-deficient cell lines.

PubMed

Wei, Shu-Chen; Lin, Young-Sun; Tsao, Po-Nien; Wu-Tsai, Jyy-Ji; Wu, C H Herbert; Wong, Jau-Min

2004-08-01

The adenomatous polyposis coli (APC) and mismatch repair (MMR) pathways are both involved in the tumorigenesis of hereditary colorectal cancers. Chemoprevention focuses on the APC pathway in the absence of information concerning MMR targets. This study compared the anticancer effects of sulindac, celecoxib, curcumin, and nifedipine in MMR-deficient cell lines, in order to determine the most appropriate chemopreventive agent for long-term use in patients with hereditary colorectal cancer. Five human colorectal cell lines (SW480, HCT116, LoVo, SW48, and HCT15) and an endometrial cancer cell line (HEC-1-A) were used for susceptibility testing. Tests included assays for growth inhibition, cell-cycle arrest, and apoptosis. Sulindac, celecoxib, curcumin, and nifedipine all displayed dose- and time-dependent anti-proliferation activities. Celecoxib was the most effective anti-proliferative agent, and increased the G0/G1 phase proportion in the cell cycle after treatment more significantly than the other agents in all cell lines. Curcumin displayed a more potent apoptosis-inducing activity than the other agents in treated cells. The tested drugs were effective against colorectal and endometrial cancer cell lines. Celecoxib is more potent with fewer side effects than sulindac. Nifedipine's observed chemopreventive efficacy may complement its known therapeutic application in patients with hypertension.

Bioconcentration of ibuprofen in fathead minnow (Pimephales promelas) and channel catfish (Ictalurus punctatus).

PubMed

Nallani, Gopinath C; Paulos, Peter M; Constantine, Lisa A; Venables, Barney J; Huggett, Duane B

2011-09-01

Pharmaceutical products and their metabolites are being widely detected in aquatic environments and there is a growing interest in assessing potential risks of these substances to fish and other non-target species. Ibuprofen is one of the most commonly used analgesic drugs and no peer-reviewed laboratory studies have evaluated the tissue specific bioconcentration of ibuprofen in fish. In the current study, fathead minnow (Pimephales promelas) were exposed to 250 μg L(-1) ibuprofen for 28 d followed by a 14 d depuration phase. In a minimized bioconcentration test design, channel catfish (Ictalurus punctatus) were exposed to 250 μg L(-1) for a week and allowed to depurate for 7 d. Tissues were collected during uptake and depuration phases of each test and the corresponding proportional and kinetic bioconcentration factors (BCFs) were estimated. The results indicated that the BCF levels were very low (0.08-1.4) implying the lack of bioconcentration potential for ibuprofen in the two species. The highest accumulation of ibuprofen was observed in the catfish plasma as opposed to individual tissues. The minimized test design yielded similar bioconcentration results as those of the standard test and has potential for its use in screening approaches for pharmaceuticals and other classes of chemicals. Copyright © 2011 Elsevier Ltd. All rights reserved.

Effects of dexamethasone, celecoxib, and methotrexate on the histology and metabolism of bone tissue in healthy Sprague Dawley rats.

PubMed

Liu, Yanzhi; Cui, Yang; Chen, Yan; Gao, Xiang; Su, Yanjie; Cui, Liao

2015-01-01

To investigate the long-term effects of three antiarthritics, namely dexamethasone, celecoxib, and methotrexate on the histology and metabolism of intact bone tissue in rats. Thirty-two 12-week-old healthy female Sprague Dawley rats were randomly allocated into four groups: 1) control (saline, daily); 2) dexamethasone (2 mg/kg, twice weekly); 3) celecoxib (50 mg/kg, daily); and 4) methotrexate (0.5 mg/kg, twice weekly). The drugs were administered to the rats for 12 weeks and the animals were weighed on a weekly basis. The femurs and lumbar vertebrae were harvested for bone mineral density and bone mechanical properties analyses. The proximal tibiae were processed for bone histomorphometry and micro-computed tomography analyses. The following results were obtained: 1) dexamethasone strongly inhibited bone formation rate accompanied with a decrease in bone mineral density and bone biomechanical properties; 2) celecoxib stimulated bone resorption, leading to a decrease of bone mass and femur biomechanic properties; and 3) methotrexate caused bone loss and bone quality deterioration to a lesser extent due to the increase of the bone turnover rate on the proximal tibial metaphysis of the rats. This study provides a comparative profile of the long-term effects of clinical doses of celecoxib, methotrexate, and dexamethasone on intact skeletons of the rats. The results indicate that the three antiarthritics have varying degrees of side effects on bone metabolism, and these findings will help physicians to learn more about the potential effects of antiarthritics on bone metabolism.

Biowaiver monographs for immediate release solid oral dosage forms: ibuprofen.

PubMed

Potthast, H; Dressman, J B; Junginger, H E; Midha, K K; Oeser, H; Shah, V P; Vogelpoel, H; Barends, D M

2005-10-01

Literature data are reviewed on the properties of ibuprofen related to the biopharmaceutics classification system (BCS). Ibuprofen was assessed to be a BCS class II drug. Differences in composition and/or manufacturing procedures were reported to have an effect on the rate, but not the extent of absorption; such differences are likely to be detectable by comparative in vitro dissolution tests. Also in view of its therapeutic use, its wide therapeutic index and uncomplicated pharmacokinetic properties, a biowaiver for immediate release (IR) ibuprofen solid oral drug products is scientifically justified, provided that the test product contains only those excipients reported in this paper in their usual amounts, the dosage form is rapidly dissolving (85% in 30 min or less) in buffer pH 6.8 and the test product also exhibits similar dissolution profiles to the reference product in buffer pH 1.2, 4.5, and 6.8. Copyright (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association

Potential of Essential Oils as Penetration Enhancers for Transdermal Administration of Ibuprofen to Treat Dysmenorrhoea.

PubMed

Chen, Jun; Jiang, Qiu-Dong; Wu, Ye-Ming; Liu, Pei; Yao, Jun-Hong; Lu, Qing; Zhang, Hui; Duan, Jin-Ao

2015-10-07

The present study was conducted to evaluate and compare five essential oils (EOs) as penetration enhancers (PEs) to improve the transdermal drug delivery (TDD) of ibuprofen to treat dysmenorrhoea. The EOs were prepared using the steam distillation method and their chemical compositions were identified by GC-MS. The corresponding cytotoxicities were evaluated in epidermal keartinocyte HaCaT cell lines by an MTT assay. Furthermore, the percutaneous permeation studies were carried out to compare the permeation enhancement effect of EOs. Then the therapeutic efficacy of ibuprofen with EOs was evaluated using dysmenorrheal model mice. The data supports a decreasing trend of skin cell viability in which Clove oil >Angelica oil > Chuanxiong oil > Cyperus oil > Cinnamon oil > Azone. Chuanxiong oil and Angelica oil had been proved to possess a significant permeation enhancement for TDD of ibuprofen. More importantly, the pain inhibitory intensity of ibuprofen hydrogel was demonstrated to be greater with Chuanxiong oil when compared to ibuprofen without EOs (p < 0.05). The contents of calcium ion and nitric oxide (NO) were also significantly changed after the addition of Chuanxiong oil (p < 0.05). In summary, we suggest that Chuanxiong oil should be viewed as the best PE for TDD of ibuprofen to treat dysmenorrhea.

Combined use of crystalline sodium salt and polymeric precipitation inhibitors to improve pharmacokinetic profile of ibuprofen through supersaturation.

PubMed

Terebetski, Jenna L; Cummings, John J; Fauty, Scott E; Michniak-Kohn, Bozena

2014-10-01

To maximize the pharmacological effect of a pain reliever such as ibuprofen, early onset of action is critical. Unfortunately, the acidic nature of ibuprofen minimizes the amount of drug that can be solubilized under gastric conditions and would be available for immediate absorption upon entry into the intestine. Although the sodium salt of ibuprofen has higher solubility, rapid conversion from the salt to the poorly soluble free acid phase occurs under gastric conditions. Therefore, the combination of the highly soluble sodium salt form of ibuprofen with polymers was evaluated as an approach to prolong supersaturation of ibuprofen during the disproportionation of the salt. Binary combinations of ibuprofen sodium with polymers resulted in the identification of several formulations that demonstrated high degrees and extended durations of supersaturation during in vitro dissolution experiments. These formulations included HPMC, polyvinyl pyrrolidone-vinyl acetate copolymer (PVP-VA64), methylcellulose (MC), and hydroxypropyl cellulose (HPC). The in vitro supersaturation observed with these ibuprofen-polymer formulations translated to an increase in Cmax and an earlier Tmax for the PVP-VA64, MC, and HPC formulations relative to ibuprofen only controls when administered orally to rats under fasted conditions. Based on these observations, combining ibuprofen sodium with polymers such as PVP-VA64, MC, or HPC is a viable formulation approach to prolong supersaturation in the stomach and enable an optimized pharmacokinetic profile in vivo where rapid onset of action is desired.

Comparative effectiveness and safety of indomethacin versus ibuprofen for the treatment of patent ductus arteriosus

PubMed Central

Gulack, Brian C.; Laughon, Matthew M.; Clark, Reese H.; Sankar, Meera N.; Hornik, Christoph P.; Smith, P. Brian

2015-01-01

Background Patent ductus arteriosus (PDA) is common in extremely premature infants and associated with increased morbidity and mortality. Medical management of PDA uses either indomethacin or ibuprofen. Despite numerous studies, uncertainty exists as to which drug is safer or more effective; we sought to fill this knowledge gap. Methods We identified infants <28 weeks gestational age discharged from neonatal intensive care units included in the Pediatrix Medical Group Clinical Data Warehouse between 2006 and 2012 who were treated with indomethacin or ibuprofen between postnatal day 2 and 14. Infants treated with both drugs or infants with a congenital malformation were excluded. We used multivariable logistic regression to determine the association of indomethacin versus ibuprofen on clinical outcomes. Results Of 6349 patients who met study criteria, 1177 (19%) received ibuprofen and 5172 (81%) received indomethacin. The median gestational age was 25 weeks (interquartile range 24–26), and 2894 (46%) infants were <750 g at birth. On unadjusted analysis, infants who received ibuprofen had significantly higher incidences of death prior to discharge, surgical ligation of the PDA prior to discharge, death or spontaneous intestinal perforation within 7 days of therapy, death or surgical ligation of the PDA prior to discharge, and an elevated creatinine within 7 days of treatment. However, on multivariable analysis, no significant differences in outcomes were observed (odds ratio for death/PDA ligation for ibuprofen vs. indomethacin = 1.12 [95% CI 0.91–1.39]). Conclusions We observed similar effectiveness and safety profiles for indomethacin and ibuprofen in the medical management of PDA in premature infants. PMID:26386610

Solubilization of ibuprofen with β-cyclodextrin derivatives: energetic and structural studies.

PubMed

di Cagno, Massimiliano; Stein, Paul C; Skalko-Basnet, Nataša; Brandl, Martin; Bauer-Brandl, Annette

2011-06-01

The aim of this work was to investigate the complexation of ibuprofen as model drug with various β-cyclodextrins (native β-cyclodextrin, hydroxypropyl-β-cyclodextrin with two different molar degrees of substitution, and methyl-β-cyclodextrin). Solutions of the commercially available β-cyclodextrins were prepared in phosphate buffer (73mM). The pH value was adjusted to 7.4 and the solutions were isotonized with NaCl. A solution of ibuprofen was prepared in the same way. A thermal activity monitor was used for isothermal titration calorimetry (ITC). (1)H NMR analysis was employed to investigate the structures of the complexes. ITC analysis showed that each type of β-cyclodextrin had its characteristic values of both enthalpy and mass equilibrium constant for the complexation processes with the drug molecules. (1)H NMR spectroscopy of the complexes showed through significant differences in chemical shifts that the physical interaction between the cyclodextrins and ibuprofen molecules were also different, probably due to different three-dimensional arrangements of ibuprofen in the cyclodextrin cavity, induced by the different substituents bonded to the glucose rings. These differences were connected to the thermodynamic parameters of the complexes. Copyright © 2011 Elsevier B.V. All rights reserved.

High-Dose Oral Ibuprofen in Treatment of Patent Ductus Arteriosus in Full-Term Neonates.

PubMed

Pourarian, Shahnaz; Rezaie, Mehrdad; Amoozgar, Hamid; Shakiba, Ali-Mohammad; Edraki, Mohammad-Reza; Mehdizadegan, Nima

2015-08-01

Patent ductus arteriosus (PDA) is an important risk for heart failure due to left to right shunt in term neonates. In this study, we evaluated the effect of high dose ibuprofen in closure of PDA in term neonates. We used double dose ibuprofen (20 mg/kg, 10 mg/kg, and 10 mg/kg) for 3 - 30 day old term neonates with PDA who were admitted in the neonatal wards of Shiraz University of Medical Sciences. The results of this study were compared to the data of the previous study in our center which used the low dose of ibuprofen (10 mg/kg, 5 mg/kg, and 5 mg/kg). 29 full term neonates received high-dose ibuprofen, in 18 neonates, PDA was closed after 4 days (62.1% versus 43.3% for the standard dose and 4.7% for the control group in the previous study) (P = 0.001). The results showed no significant correlation between the closure rate and gestational age, postnatal age, sex, and weight. In the 4(th) day of treatment, size of the pulmonic end of ductus arteriosus decreased from 2.09 mm to 0.77 mm compared to 1.68 mm to 0.81 mm in the standard dose of oral ibuprofen and 2.1 mm to 1.4 mm in the control group (P = 0.046). This study indicated that high-dose oral ibuprofen was more effective in closing or decreasing the size of PDA.

Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations.

PubMed

Friedman, H; Seckman, C; Stubbs, C; Oster, H; Royer, G

1990-01-01

This multiple-dose, double-blind, placebo-controlled, randomized, normal volunteer study compared formulations of ibuprofen/codeine and aspirin/codeine for systemic safety. Vital signs, hematologic, biochemical and urinary parameters, side effects, mood and mental alertness, were monitored. The placebo group had less gastrointestinal side effects and more frequent stools than the active treatment groups. There was statistical evidence for greater adverse effects of aspirin/codeine on mood and mental alertness in comparison to ibuprofen/codeine and placebo. Ibuprofen/codeine had a more favorable adverse effect profile than aspirin/codeine. A mild respiratory and cardiac depressant effect attributable to codeine was evident in all active treatment groups after 7 days of frequent therapy. More work needs to be done to elucidate the factors regulating the development of tolerance to the respiratory and cardiovascular depressant effects of opiates in general, and for codeine in particular.

Efficacy and safety of oral versus intravenous ibuprofen in very low birth weight preterm infants with patent ductus arteriosus.

PubMed

Gokmen, Tulin; Erdeve, Omer; Altug, Nahide; Oguz, Serife Suna; Uras, Nurdan; Dilmen, Ugur

2011-04-01

To compare oral ibuprofen with intravenous ibuprofen for closure of patent ductus arteriosus in very low birth weight (VLBW) preterm infants. In a prospective, randomized study, 102 VLBW preterm infants with patent ductus arteriosus received either intravenous or oral ibuprofen at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 hours. The success rate and evaluation of renal tolerance using cystatin-C were the major outcomes. Patent ductus arteriosus closure rate was significantly higher with oral ibuprofen (84.6% versus 62%) after the first course of the treatment (P = .011). The cystatin-C level increased significantly after treatment in the oral group (P = .001), but did not change with intravenous ibuprofen (P = .4). Oral ibuprofen is more effective than intravenous ibuprofen for ductal closure in VLBW infants. The increase in the cystatin-C level with oral treatment suggests that patients with borderline renal function should be evaluated and followed closely. Copyright © 2011 Mosby, Inc. All rights reserved.

Enhanced Longevity by Ibuprofen, Conserved in Multiple Species, Occurs in Yeast through Inhibition of Tryptophan Import

PubMed Central

He, Chong; Tsuchiyama, Scott K.; Nguyen, Quynh T.; Plyusnina, Ekaterina N.; Terrill, Samuel R.; Sahibzada, Sarah; Patel, Bhumil; Faulkner, Alena R.; Shaposhnikov, Mikhail V.; Tian, Ruilin; Tsuchiya, Mitsuhiro; Kaeberlein, Matt; Moskalev, Alexey A.; Kennedy, Brian K.; Polymenis, Michael

2014-01-01

The common non-steroidal anti-inflammatory drug ibuprofen has been associated with a reduced risk of some age-related pathologies. However, a general pro-longevity role for ibuprofen and its mechanistic basis remains unclear. Here we show that ibuprofen increased the lifespan of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster, indicative of conserved eukaryotic longevity effects. Studies in yeast indicate that ibuprofen destabilizes the Tat2p permease and inhibits tryptophan uptake. Loss of Tat2p increased replicative lifespan (RLS), but ibuprofen did not increase RLS when Tat2p was stabilized or in an already long-lived strain background impaired for aromatic amino acid uptake. Concomitant with lifespan extension, ibuprofen moderately reduced cell size at birth, leading to a delay in the G1 phase of the cell cycle. Similar changes in cell cycle progression were evident in a large dataset of replicatively long-lived yeast deletion strains. These results point to fundamental cell cycle signatures linked with longevity, implicate aromatic amino acid import in aging and identify a largely safe drug that extends lifespan across different kingdoms of life. PMID:25521617

Ibuprofen-in-cyclodextrin-in-W/O/W emulsion - Improving the initial and long-term encapsulation efficiency of a model active ingredient.

PubMed

Hattrem, Magnus N; Kristiansen, Kåre A; Aachmann, Finn L; Dille, Morten J; Draget, Kurt I

2015-06-20

A challenge in formulating water-in-oil-in-water (W/O/W) emulsions is the uncontrolled release of the encapsulated compound prior to application. Pharmaceuticals and nutraceuticals usually have amphipathic nature, which may contribute to leakage of the active ingredient. In the present study, cyclodextrins (CyDs) were used to impart a change in the relative polarity and size of a model compound (ibuprofen) by the formation of inclusion complexes. Various inclusion complexes (2-hydroxypropyl (HP)-β-CyD-, α-CyD- and γ-CyD-ibuprofen) were prepared and presented within W/O/W emulsions, and the initial and long-term encapsulation efficiency was investigated. HP-β-CyD-ibuprofen provided the highest encapsulation of ibuprofen in comparison to a W/O/W emulsion with unassociated ibuprofen confined within the inner water phase, with a four-fold increase in the encapsulation efficiency. An improved, although lower, encapsulation efficiency was obtained for the inclusion complex γ-CyD-ibuprofen in comparison to HP-β-CyD-ibuprofen, whereas α-CyD-ibuprofen had a similar encapsulation efficiency to that of unassociated ibuprofen. The lower encapsulation efficiency of ibuprofen in combination with α-CyD and γ-CyD was attributed to a lower association constant for the γ-CyD-ibuprofen inclusion complex and the ability of α-CyD to form inclusion complexes with fatty acids. For the W/O/W emulsion prepared with HP-β-CyD-ibuprofen, the highest encapsulation of ibuprofen was obtained at hyper- and iso-osmotic conditions and by using an excess molar ratio of CyD to ibuprofen. In the last part of the study, it was suggested that the chemical modification of the HP-β-CyD molecule did not influence the encapsulation of ibuprofen, as a similar encapsulation efficiency was obtained for an inclusion complex prepared with mono-1-glucose-β-CyD. Copyright © 2015 Elsevier B.V. All rights reserved.

Osteoarthritis of the knee and hip. Part II: therapy with ibuprofen and a review of clinical trials.

PubMed

Adatia, Aleem; Rainsford, K D; Kean, Walter F

2012-05-01

We review the pharmacological properties and clinical evidence pertaining to the efficacy of ibuprofen as a first-line treatment in hip and knee osteoarthritis (OA). In the context of our previous paper's exploration of the aetiology and pathogenesis of OA as a basis for pharmacotherapy, we discuss the pharmacokinetics (PK) and clinical pharmacodynamics (PD) of ibuprofen relevant to OA. Although widely used, the benefits and risks of ibuprofen, especially compared with other non-steroidal anti-inflammatory drugs (NSAIDs) and placebo, have only recently been evaluated in OA of the hip and knee in randomized-controlled clinical trials (RCT). The efficacy and occurrence of adverse reactions from ibuprofen was compared with placebo in a structural review of the literature and systematic review of RCTs in large-scale clinical trials. Ibuprofen has been found to result in approximately 50-60% improvement over placebo in WOMAC scores, including those reflecting inflammatory joint pain in knee and hip OA or other indices of pain, disability and impaired function. Mega-trials performed in comparison with the newer NSAIDs, the coxibs, have shown that ibuprofen has comparable therapeutic benefits and although serious gastrointestinal conditions are sometimes more frequent after short-term treatment, longer-term (several months) therapy in OA reduces the advantages of the coxibs over other NSAIDs including ibuprofen. Cardiovascular risk, though present with coxibs and some NSAIDs in OA, is lower or slightly so with ibuprofen compared with coxibs. Ibuprofen is effective and relatively safe (especially at low over-the-counter doses and in the short term) for mild-to-moderate OA of the knee and hip. The PK properties of ibuprofen in OA (short plasma t½) confer advantages of this drug for OA, while evidence for clinically relevant PD benefits in joints of patients with OA, though limited, is suggestive of local anti-inflammatory activity. © 2012 The Authors. JPP © 2012 Royal

p53 is important for the anti-proliferative effect of ibuprofen in colon carcinoma cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janssen, Astrid; Schiffmann, Susanne; Birod, Kerstin

2008-01-25

S-ibuprofen which inhibits the cyclooxygenase-1/-2 and R-ibuprofen which shows no COX-inhibition at therapeutic concentrations have anti-carcinogenic effects in human colon cancer cells; however, the molecular mechanisms for these effects are still unknown. Using HCT-116 colon carcinoma cell lines, expressing either the wild-type form of p53 (HCT-116 p53{sup wt}) or being p(HCT-116 p53{sup -/-}), we demonstrated that both induction of a cell cycle block and apoptosis after S- and R-ibuprofen treatment is in part dependent on p53. Also in the in vivo nude mice model HCT-116 p53{sup -/-} xenografts were less sensitive for S- and R-ibuprofen treatment than HCT-116 p53{sup wt}more » cells. Furthermore, results indicate that induction of apoptosis in HCT-116 p53{sup wt} cells after ibuprofen treatment is in part dependent on a signalling pathway including the neutrophin receptor p75{sup NTR}, p53 and Bax.« less

Concurrent use of methotrexate and celecoxib increases risk of silent liver fibrosis in rheumatoid arthritis patients with subclinical reduced kidney function.

PubMed

Park, Jin Su; Park, Min-Chan; Park, Yong-Beom; Lee, Soo-Kon; Lee, Sang-Won

2014-01-01

We evaluated the effects of concurrent use of methotrexate and celecoxib on silent liver and kidney damages in rheumatoid arthritis (RA) patients. We enrolled 92 RA patients with normal laboratory results related to liver and kidney functions, who had received methotrexate and celecoxib concurrently over 6 months. Liver stiffness measurement (LSM) using transient elastography and ultrasonography were performed along with blood and urine tests. Estimated glomerular filtration rate (eGFR) was calculated by both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and the Modification of Diet in Renal Disease (MDRD) equations. Initial eGFR represented kidney function at the time of the initiation of celecoxib. The cutoff for abnormal LSM values was adopted as 5.3 kPa. The optimal cutoff of each eGFR for abnormal LSM values was also calculated. The median age of patients was 55 years old (74 women). The median LSM was 4.4 kPa and the median eGFRs and median initial eGFRs ranged from 89 to 99 mL/min/1.73 m(2). The cumulative doses of methotrexate and celecoxib and their concurrent administration duration did not affect LSM values and eGFRs. Both eGFRs were significantly associated with LSM values. Patients with initial eGFR(CKD-EPI), initial eGFR(MDRD), and eGFR(CKD-EPI) below each optimal cutoff had significantly high risks for silent liver fibrosis (RR 9.4, 10.3, and 4.4, p < 0.001, respectively). Both initial eGFRs (CKD-EPI and MDRD) and eGFR (CKD-EPI) were significant predictors for the development of silent liver fibrosis in RA patients who had received methotrexate and celecoxib concurrently for at least 6 months.

Cocrystal Screening of Ibuprofen with Oxalic Acid and Citric Acid via Grinding Method

NASA Astrophysics Data System (ADS)

Othman, M. F.; Anuar, N.; Rahman, S. Ad; Taifuddin, N. A. Ahmad

2018-05-01

Ibuprofen is a Class II Biological Safety Class (BSC) drugs used for relief of arthritis, as an analgesic and possesses the effect of antiplatelet. The major problem involves in ibuprofen is it has a low solubility and high permeability thus causes an unsatisfactory therapeutic effect to humans. Thus, in this work, alteration of ibuprofen’s physicochemical properties is conducted by means of cocrystallization technique. Co-crystallizations of ibuprofen were prepared with selected coformers using dry grinding and liquid assisted grinding (LAG) techniques in different molar ratios while ethanol and propanol were used as a solvent. The new crystalline forms were identified and characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and fourier transform infrared spectroscopy (FTIR). Analysis for Ibuprofen-Citric acid (IBP-CA) system, co-crystal was successfully formed in 1:2, 1:3, 2:1 and 3:1 molar ratios for neat grinding method although the co-crystal produced is unstable. Meanwhile, for Ibuprofen-Oxalic acid (IBP-OA) system, the co-crystal formation was identified only in 1:1, 1:2 and 1:3 molar ratios for the neat grinding method. LAG method shows that co-crystal formation was unsuccessful in both solvents for IBP-CA, while IBP-OA co-crystal was formed in the molar ratio 1:1, 2:1 and 3:1 in ethanol, and 2:1 and 3:1 in propanol.

Study of particle rearrangement, compression behavior and dissolution properties after melt dispersion of ibuprofen, Avicel and Aerosil

PubMed Central

Mallick, Subrata; Kumar Pradhan, Saroj; Chandran, Muronia; Acharya, Manoj; Digdarsini, Tanmayee; Mohapatra, Rajaram

2011-01-01

Particle rearrangements, compaction under pressure and in vitro dissolution have been evaluated after melt dispersion of ibuprofen, Avicel and Aerosil. The Cooper–Eaton and Kuno equations were utilized for the determination of particle rearrangement and compression behavior from tap density and compact data. Particle rearrangement could be divided into two stages as primary and secondary rearrangement. Transitional tapping between the stages was found to be 20–25 taps in ibuprofen crystalline powder, which was increased up to 45 taps with all formulated powders. Compaction in the rearrangement stages was increased in all the formulations with respect to pure ibuprofen. Significantly increased compaction of ibuprofen under pressure can be achieved using Avicel by melt dispersion technique, which could be beneficial in ibuprofen tablet manufacturing by direct compression. SEM, FTIR and DSC have been utilized for physicochemical characterization of the melt dispersion powder materials. Dissolution of ibuprofen from compacted tablet of physical mixture and melt dispersion particles has also been improved greatly in the following order: Ibc

Chronic ibuprofen administration reduces neuropathic pain but does not exert neuroprotection after spinal cord injury in adult rats.

PubMed

Redondo-Castro, Elena; Navarro, Xavier

2014-02-01

Ibuprofen is commonly used as an anti-inflammatory analgesic drug, although it is not amongst the first-line treatments for neuropathic pain. Its main effects are mediated by non-specific inhibition of COX enzymes, but it also exerts some COX-independent effects, such as the inhibition of RhoA signaling and the modulation of glial activity. These effects have boosted the use of ibuprofen as a tool to promote axonal regeneration and to increase functional recovery after neural injuries, although with controversial results showing positive and negative outcomes of ibuprofen treatment in several experimental models. We have evaluated the effects of ibuprofen administered at 60 mg/kg twice a day to rats subjected to a mild spinal cord contusion. Our results indicate that ibuprofen ameliorates mechanical hyperalgesia in rats by reducing central hyperexcitability, but failed to produce improvements in the recovery of locomotion. Despite an early effect on reducing microglial reactivity, the ibuprofen treatment did not provide histological evidence of neuroprotection; indeed the volume of cord tissue spared rostral to the lesion was decreased in ibuprofen treated rats. In summary, the early modulation of neuroinflammation produced by the administration of ibuprofen seems to eventually lead to a worse resolution of detrimental events occurring in the secondary injury phase, but also to reduce the development of neuropathic pain. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of upper respiratory tract illnesses, ibuprofen and caffeine on reaction time and alertness.

PubMed

Smith, Andrew P; Nutt, David J

2014-05-01

Compared with healthy individuals, those with upper respiratory tract illnesses (URTIs) report reduced alertness and have slower reaction times. It is important to evaluate medication that can remove this behavioural malaise. The aim of this study was to compare the effects of a combination of ibuprofen plus caffeine with ibuprofen and caffeine alone, and placebo on malaise associated with URTIs, as measured by psychomotor performance and mood testing. Volunteers were randomly assigned to one of four medication conditions as follows: 200 mg ibuprofen and 100 mg caffeine; 200 mg ibuprofen; 100 mg caffeine; placebo. A single oral dose was given and testing followed for 3 h. Efficacy variables were based on the volunteers' performance, measured by psychomotor performance and mood. The pre-drug results confirmed that those with an URTI had a more negative mood and impaired performance. Results from the simple reaction time task, at both 55- and 110-min post-dosing, showed that a single-dose of caffeinated products (I200/C100 and CAF100) led to significantly faster reaction times than IBU200 and placebo. These effects were generally confirmed with the other performance tasks. Subjective measures showed that the combination of ibuprofen and caffeine was superior to the other conditions. There were no serious adverse events reported, and study medication was well tolerated. The results from the post-drug assessments suggest that a combination of ibuprofen and caffeine was the optimum treatment for malaise associated with URTIs in that it had significant effects on objective performance and subjective measures.

Spectrofluorimetric study of host-guest complexation of ibuprofen with β-cyclodextrin and its analytical application

NASA Astrophysics Data System (ADS)

Manzoori, Jamshid L.; Amjadi, Mohammad

2003-03-01

The characteristics of host-guest complexation between β-cyclodextrin (β-CD) and two forms of ibuprofen (protonated and deprotonated) were investigated by fluorescence spectrometry. 1:1 stoichiometries for both complexes were established and their association constants at different temperatures were calculated by applying a non-linear regression method to the change in the fluorescence of ibuprofen that brought about by the presence of β-CD. The thermodynamic parameters (Δ H, Δ S and Δ G) associated with the inclusion process were also determined. Based on the obtained results, a sensitive spectrofluorimetric method for the determination of ibuprofen was developed with a linear range of 0.1-2 μg ml -1 and a detection limit of 0.03 μg ml -1. The method was applied satisfactorily to the determination of ibuprofen in pharmaceutical preparations.

Utilization of supercritical carbon dioxide for complex formation of ibuprofen and methyl-beta-cyclodextrin.

PubMed

Charoenchaitrakool, M; Dehghani, F; Foster, N R

2002-06-04

The dissolution rate of a drug into the biological environment can be enhanced by forming complexes with cyclodextrins and their derivatives. In this study, ibuprofen-methyl-beta-cyclodextrin complexes were prepared successfully by passing ibuprofen-laden CO(2) through a methyl-beta-cyclodextrin packed bed. The maximum drug loading obtained in this work was 10.8 wt.%, which was comparable to that of a 1:1 complex (13.6 wt.% of ibuprofen). The complex exhibited instantaneous dissolution profiles in water solution. The enhanced dissolution rate was attributed to the amorphous character and improved wettability of the product.

Ibuprofen transport into and through skin from topical formulations: in vitro-in vivo comparison.

PubMed

Herkenne, Christophe; Naik, Aarti; Kalia, Yogeshvar N; Hadgraft, Jonathan; Guy, Richard H

2007-01-01

The goal was to compare ibuprofen transport into and through skin in vivo in man and in vitro (across silicone membranes and freshly excised pig skin) from four marketed formulations. Ibuprofen gels were administered in vivo for 30 minutes. The stratum corneum (SC) at the application site was then tape-stripped, quantified gravimetrically, and extracted for drug analysis. Together with concomitant transepidermal water loss measurements, SC drug concentration-depth profiles were reproducibly determined and fitted mathematically to obtain a partition coefficient, a first-order rate constant related to ibuprofen diffusivity, and the total drug amount in the SC at the end of the application. All derived parameters were consistent across formulations. Ibuprofen permeation data through both silicone membrane and pig ear skin were also fitted to yield partitioning and diffusion parameters. The former revealed that ibuprofen partitioned differently from the gels into this model barrier. Across pig skin, however, better correlation with in vivo results was found. The dermatopharmacokinetic approach, using SC tape-stripping, offers a valid method to assess equivalency between topical drug formulations. In vitro experiments must be extrapolated cautiously to the clinic, especially when complex interactions between real formulations, which deliver both drug and excipients, and the skin occur.

Enantioselective CE method for pharmacokinetic studies on ibuprofen and its chiral metabolites with reference to genetic polymorphism.

PubMed

Główka, Franciszek; Karaźniewicz, Marta

2007-08-01

A stereospecific CE method was elaborated for the quantification of ibuprofen enantiomers and their major phase I metabolites: 2'-hydroxy-ibuprofen and 2'-carboxy-ibuprofen in plasma and urine. Optimal temperature and pH of BGE were established to obtain complete separation of eight ibuprofen chiral compounds and (+)-S indobufen, applied as an internal standard, during one analytical run. After isolation from biological matrices using SPE on an octadecyl stationary phase, the analytes were separated and resolved up to 10 min in a silica capillary filled with BGE, consisting of heptakis 2,3,6-tri-O-methyl-beta-CD in triethanolamine-phosphate buffer, pH 5.0. Complete enantioseparation of the all analytes confirmed specificity of the method. The calibration curves were linear in the range of 0.1-25.0 mg/L for IBP enantiomers and their chiral metabolites in 0.5 mL of plasma and 1.0-200.0 mg/L in 0.05 mL of urine. Following SPE procedure, recovery of the chiral analytes from the two media was in the ranges of 82-87%, 90-95% and 70-76% for ibuprofen, 2'-hydroxy-ibuprofen and 2'-carboxy-ibuprofen enantiomers, respectively. The validated method was successfully applied in pharmacokinetic investigations of IBP enantiomers as well as free chiral metabolites in reference to the genetic polymorphism of CYP450 2C isoenzymes.

Ibuprofen versus acetaminophen as a post-partum analgesic for women with severe pre-eclampsia: randomized clinical study.

PubMed

Vigil-De Gracia, Paulino; Solis, Valentin; Ortega, Nelson

2017-06-01

To compare differences in blood pressure levels between patients with severe post-partum pre-eclampsia using ibuprofen or acetaminophen. A randomized controlled trial was made in women with severe pre-eclampsia or superimposed pre-eclampsia after vaginal birth. The patient was randomly selected to receive either 400 mg of ibuprofen every 8 h or 1 g of acetaminophen every 6 h during the post-partum. The primary variable was systolic hypertension ≥150 mmHg and/or diastolic hypertension ≥100 mmHg after the first 24 h post-partum. Secondary variables were the arterial blood pressure readings at 24, 48, 72, and 96 h post-partum and maternal complications. A total of 113 patients were studied: 56 in the acetaminophen group and 57 in the ibuprofen group. With regard to the primary outcome, more cases were significantly hypertensive in the ibuprofen group (36/57; 63.1%) than in the acetaminophen group (16/56; 28.6%). Severe hypertension (≥160/110 mmHg) was not significantly different between the groups, 14.5% (acetaminophen) and 24.5% (ibuprofen). The levels of arterial blood pressure show a hammock-shaped curve independent of the drug used, however, is more noticeable with ibuprofen. This study shows that ibuprofen significantly elevates blood pressure in women with severe pre-eclampsia during the post-partum period.

Differing disintegration and dissolution rates, pharmacokinetic profiles and gastrointestinal tolerability of over the counter ibuprofen formulations.

PubMed

Bjarnason, Ingvar; Sancak, Ozgur; Crossley, Anne; Penrose, Andrew; Lanas, Angel

2018-02-01

Formulations of over the counter (OTC) NSAIDs differ substantially, but information is lacking on whether this alters their gastrointestinal profiles. To assess disintegration and dissolution rates and pharmacokinetics of four preparations of OTC ibuprofen and relate these with spontaneously reported gastrointestinal adverse events. Disintegration and dissolution rates of ibuprofen tablets as (a) acid, (b) sodium salt, (c) lysine salt, and (d) as a liquid gelatine capsule were assessed. Pharmacokinetic data gastrointestinal and spontaneously reported adverse events arising from global sales were obtained from files from Reckitt Benckiser. Disintegration at low pH was progressively shorter for the preparations from a-to-d with formation of correspondingly smaller ibuprofen crystals, while dissolution was consistently poor. Dissolution at a neutral pH was least rapid for the liquid gelatine capsule. Pharmacokinetic data showed a shorter t max and a higher C max for preparations b-d as compared with ibuprofen acid. Spontaneously reported abdominal symptoms were rare with the liquid gelatine preparation. The formulations of OTC ibuprofen differ in their disintegration and dissolution properties, pharmacokinetic profiles and apparent gastrointestinal tolerability. Spontaneously reported abdominal symptoms were five times lower with the liquid gelatine capsule as compared with ibuprofen acid despite a 30% increase in C max . © 2017 Royal Pharmaceutical Society.

Celecoxib can suppress expression of genes associated with PGE2 pathway in chondrocytes under inflammatory conditions.

PubMed

Sun, Tian-Wen; Wu, Zhi-Hong; Weng, Xi-Sheng

2015-01-01

This study aimed to investigate the effect of a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) on the expression of arachidonate-associated inflammatory genes in cultured human normal chondrocytes. Normal chondrocytes were obtained from the cartilage of three different amputated patients without osteoarthritis (OA). Affymetrix Human microarray was used to assess the alterations in gene expression in three groups of cells: untreated cells (negative control group), cells treated with interleukin-1β (IL-1β) (positive control group), and cells treated with IL-1β and celecoxib. The patterns of up-regulation and down-regulation of gene expression were further validated by real-time PCR. A total of 1091 up-regulated genes and 1252 down-regulated genes were identified in the positive control group compared with the negative control group. Among them, PTGS2, ADAMTS5, PTGER2, mPTGES and PTGER4 are known to be involved in chondrocyte inflammation, while VEGFA, BCL2, TRAF1, CYR61, BMP6, DAPK1, DUSP7, IL1RN, MMP13 and TNFSF10 were reported being associated with cytokine and chemokine signaling. 189 up-regulated genes and 177 down-regulated genes were identified in the positive control group compared with intervention group. PTGS1, PTGS2, ADAMTS5, PTGER2, mPTGES and PTGER4 were among the genes down-regulated upon the treatment with celecoxib. Our results demonstrated that the OA chondrocytes are the site of active eicosanoid production. IL-1β can activate inflammation in chondrocytes and trigger the production of various proteins involved in cyclooxygenase pathway. The expression of genes corresponding to these proteins can be down-regulated by celecoxib. The findings indicate that the therapy with prostaglandin E2 (PGE2)-blocking agents may decrease the PGE2 production not only by direct inhibition of COX-2 activity, but also by down-regulating the expression of genes encoding for COX-2, microsomal prostaglandin-endoperoxide synthase 1 (mPGES-1) and prostaglandin

Single dose oral analgesics for acute postoperative pain in adults - an overview of Cochrane reviews.

PubMed

Moore, R Andrew; Derry, Sheena; Aldington, Dominic; Wiffen, Philip J

2015-09-28

, methods, and efficacy outcome reporting. No statistical comparison was undertaken.Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours.Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence). There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cazanave, Sophie; Vadrot, Nathalie; Tinel, Marina

Fas stimulation recruits neutrophils and activates macrophages that secrete tumor necrosis factor-{alpha} (TNF-{alpha}), which aggravates Fas-mediated liver injury. To determine whether nonsteroidal anti-inflammatory drugs modify these processes, we challenged 24-hour-fasted mice with the agonistic Jo2 anti-Fas antibody (4 {mu}g/mouse), and treated the animals 1 h later with saline or ibuprofen (250 mg/kg), a dual cyclooxygenase (COX)-1 and COX-2 inhibitor. Ibuprofen attenuated the Jo2-mediated recruitment/activation of myeloperoxidase-secreting neutrophils/macrophages in the liver, and attenuated the surge in serum TNF-{alpha}. Ibuprofen also minimized hepatic glutathione depletion, Bid truncation, caspase activation, outer mitochondrial membrane rupture, hepatocyte apoptosis and the increase in serum alanine aminotransferasemore » (ALT) activity 5 h after Jo2 administration, to finally decrease mouse mortality at later times. The concomitant administration of pentoxifylline (decreasing TNF-{alpha} secretion) and infliximab (trapping TNF-{alpha}) likewise attenuated the Jo2-mediated increase in TNF-{alpha}, the decrease in hepatic glutathione, and the increase in serum ALT activity 5 h after Jo2 administration. The concomitant administration of the COX-1 inhibitor, SC-560 (10 mg/kg) and the COX-2 inhibitor, celecoxib (40 mg/kg) 1 h after Jo2 administration, also decreased liver injury 5 h after Jo2 administration. In contrast, SC-560 (10 mg/kg) or celecoxib (40 or 160 mg/kg) given alone had no significant protective effects. In conclusion, secondary TNF-{alpha} secretion plays an important role in Jo2-mediated glutathione depletion and liver injury. The combined inhibition of COX-1 and COX-2 by ibuprofen attenuates TNF-{alpha} secretion, glutathione depletion, mitochondrial alterations, hepatic apoptosis and mortality in Jo2-treated fasted mice.« less

Ibuprofen-induced patent ductus arteriosus closure: physiologic, histologic, and biochemical effects on the premature lung.

PubMed

McCurnin, Donald; Seidner, Steven; Chang, Ling-Yi; Waleh, Nahid; Ikegami, Machiko; Petershack, Jean; Yoder, Brad; Giavedoni, Luis; Albertine, Kurt H; Dahl, Mar Janna; Wang, Zheng-ming; Clyman, Ronald I

2008-05-01

The goal was to study the pulmonary, biochemical, and morphologic effects of a persistent patent ductus arteriosus in a preterm baboon model of bronchopulmonary dysplasia. Preterm baboons (treated prenatally with glucocorticoids) were delivered at 125 days of gestation (term: 185 days), given surfactant, and ventilated for 14 days. Twenty-four hours after birth, newborns were randomly assigned to receive either ibuprofen (to close the patent ductus arteriosus; n = 8) or no drug (control; n = 13). After treatment was started, the ibuprofen group had significantly lower pulmonary/systemic flow ratio, higher systemic blood pressure, and lower left ventricular end diastolic diameter, compared with the control group. There were no differences in cardiac performance indices between the groups. Ventilation index and dynamic compliance were significantly improved with ibuprofen. The improved pulmonary mechanics in ibuprofen-treated newborns were not attributable to changes in levels of surfactant protein B, C, or D, saturated phosphatidylcholine, or surfactant inhibitory proteins. There were no differences in tracheal concentrations of cytokines commonly associated with the development of bronchopulmonary dysplasia. The groups had similar messenger RNA expression of genes that regulate inflammation and remodeling in the lung. Lungs from ibuprofen-treated newborns were significantly drier (lower wet/dry ratio) and expressed 2.5 times more epithelial sodium channel protein than did control lungs. By 14 days after delivery, control newborns had morphologic features of arrested alveolar development (decreased alveolar surface area and complexity), compared with age-matched fetuses. In contrast, there was no evidence of alveolar arrest in the ibuprofen-treated newborns. Ibuprofen-induced patent ductus arteriosus closure improved pulmonary mechanics, decreased total lung water, increased epithelial sodium channel expression, and decreased the detrimental effects of preterm birth

Failure of Ibuprofen to prevent progressive dermal ischemia after burning in guinea pigs.

PubMed

Tan, Qian; Lin, Zihao; Ma, Wenxi; Chen, Huairen; Wang, Lei; Ning, Guansen; Zhou, Xu

2002-08-01

It is controversial whether the use of prostaglandin inhibitors could prevent progressive dermal ischemia in the postburn stasis zone. This study evaluated the effect of Ibuprofen on preventing postburn dermal ischemia using an animal model of India ink perfusion and skin transparent preparation techniques. The closely clipped backs of the guinea pigs were bathed in 75 degrees C water for 10s. Ibuprofen-treated groups were fed intragastrically with Ibuprofen (12.5mg/kg) every 6h. All animals were perfused with 70% India ink via a cervical artery cannula at 16 kPa constant pressure at 0, 8, 16, 24h postburn. Skin transparent preparations were made, and 6-keto-PGF(1 alpha) and T x B(2) levels in skin tissue were assessed. India ink filling rates in skin capillary plexuses decreased gradually with postburn time elapsing (P<0.01). 6-keto-PGF(1 alpha) and T x B(2) levels in two groups increased. The increase of T x B(2) was dominant, which was related to postburn dermal ischemia (r=0.742, P<0.01). Though levels of 6-keto-PGF(1 alpha) and T x B(2) decreased in Ibuprofen-treated groups, India ink filling rates showed no significant difference between controls and experimental groups (P>0.05). The results were also confirmed by observation of skin transparent preparations. This study suggests that Ibuprofen has no preventive effect on progressive dermal ischemia after burning.

Spectrofluorimetric study of host-guest complexation of ibuprofen with beta-cyclodextrin and its analytical application.

PubMed

Manzoori, Jamshid L; Amjadi, Mohammad

2003-03-15

The characteristics of host-guest complexation between beta-cyclodextrin (beta-CD) and two forms of ibuprofen (protonated and deprotonated) were investigated by fluorescence spectrometry. 1:1 stoichiometries for both complexes were established and their association constants at different temperatures were calculated by applying a non-linear regression method to the change in the fluorescence of ibuprofen that brought about by the presence of beta-CD. The thermodynamic parameters (deltaH, deltaS and deltaG) associated with the inclusion process were also determined. Based on the obtained results, a sensitive spectrofluorimetric method for the determination of ibuprofen was developed with a linear range of 0.1-2 microg ml(-1) and a detection limit of 0.03 microg ml(-1). The method was applied satisfactorily to the determination of ibuprofen in pharmaceutical preparations. Copyright 2002 Elsevier Science B.V.

Solubility of (+/-)-ibuprofen and S (+)-ibuprofen in the presence of cosolvents and cyclodextrins.

PubMed

Nerurkar, Jayanti; Beach, J W; Park, M O; Jun, H W

2005-01-01

Aqueous solubility is an important parameter for the development of liquid formulations and in the determination of bioavailability of oral dosage forms. Ibuprofen (IB), a nonsteroidal anti-inflammatory drug, is a chiral molecule and is currently used clinically as a racemate (racIB). However, the S form of ibuprofen or S(+)-ibuprofen (SIB) is the biologically active isomer and is primarily responsible for the antiinflammatory activity. Phase solubility studies were carried out to compare the saturation solubilities of racIB and SIB in the presence of common pharmaceutical solvents such as glycerol, sorbitol solution, propylene glycol (PG), and polyethylene glycol (PEG 300) over the range of 20% to 80% v/v in aqueous based systems. The solubilities of the two compounds were also compared in the presence of cyclodextrins such as beta cyclodextrin (CD), hydroxypropyl beta cyclodextrin (HPCD), and beta cyclodextrin sulfobutyl ether sodium salt (CDSB) over the range of 5% to 25% w/v. Solubility determinations were carried at 25 degrees C and 37 degrees C. Cosolvents exponentially increased the solubility of both SIB and racIB, especially in the presence of PG and PEG 300. Glycerol was not very effective in increasing the aqueous solubilities of both compounds, whereas sorbitol solution had a minimal effect on their solubility. PG and PEG 300 increased the solubility of SIB by 400-fold and 1500-fold, respectively, whereas the rise in solubility for racIB was 193-fold and 700-fold, respectively, at 25 degrees C for the highest concentration of the cosolvents used (80% v/v). Of the two compounds studied, higher equilibrium solubilities were observed for SIB as compared with racIB. The derivatized cyclodextrins increased the aqueous solubility of racIB and SIB in a concentration-dependent manner giving AL type of phase diagrams. The phase solubility diagrams indicated the formation of soluble inclusion complexes between the drugs and HPCD and CDSB, which was of 1

The addition of celecoxib improves the antitumor effect of cetuximab in colorectal cancer: role of EGFR-RAS-FOXM1-β-catenin signaling axis

PubMed Central

Valverde, Araceli; Peñarando, Jon; Cañas, Amanda; López-Sánchez, Laura M.; Conde, Francisco; Guil-Luna, Silvia; Hernández, Vanessa; Villar, Carlos; Morales-Estévez, Cristina; de la Haba-Rodríguez, Juan; Arand o, Enrique; Rodríguez-Ariza, Antonio

2017-01-01

Here we showed that the addition of the COX-2 inhibitor celecoxib improved the antitumor efficacy in colorectal cancer (CRC) of the monoclonal anti-EGFR antibody cetuximab. The addition of celecoxib augmented the efficacy of cetuximab to inhibit cell proliferation and to induce apoptosis in CRC cells. Moreover, the combination of celecoxib and cetuximab was more effective than either treatment alone in reducing the tumor volume in a mouse xenograft model. The combined treatment enhanced the inhibition of EGFR signaling and altered the subcellular distribution of β-catenin. Moreover, knockdown of FOXM1 showed that this transcription factor participates in this enhanced antitumoral response. Besides, the combined treatment decreased β-catenin/FOXM1 interaction and reduced the cancer stem cell subpopulation in CRC cells, as indicated their diminished capacity to form colonospheres. Notably, the inmunodetection of FOXM1 in the nuclei of tumor cells in human colorectal adenocarcinomas was significantly associated with response of patients to cetuximab. In summary, our study shows that the addition of celecoxib enhances the antitumor efficacy of cetuximab in CRC due to impairment of EGFR-RAS-FOXM1-β-catenin signaling axis. Results also support that FOXM1 could be a predictive marker of response of mCRC patients to cetuximab therapy. PMID:28423516

Luteinized unruptured follicle syndrome increased by inactive disease and selective cyclooxygenase 2 inhibitors in women with inflammatory arthropathies.

PubMed

Micu, Mihaela C; Micu, Romeo; Ostensen, Monika

2011-09-01

Administration of nonsteroidal antiinflammatory drugs (NSAIDs) may impair fertility. The occurrence of the luteinized unruptured follicle (LUF) syndrome was assessed in women with inflammatory arthropathies exposed to NSAIDs and compared to that in nonexposed women. Fourteen patients with inflammatory rheumatic disease, 29 women with noninflammatory musculoskeletal conditions, and 449 women not exposed to NSAIDs were studied by intravaginal ultrasound monitoring for follicular development and ovulation in 1 or more menstrual cycles. Disease activity was assessed in inflammatory rheumatic disease. In 59 monitored cycles of patients with continuous NSAID exposure, 35.6% of LUF syndromes occurred compared to 3.4% of LUF syndromes in untreated women (P < 0.001). Etoricoxib was responsible for 75% of LUF syndromes in patients exposed continuously, whereas diclofenac generated 15% of LUF syndromes. An ibuprofen dosage of 1,600 mg/day did not induce LUF syndrome either at continuous periovulatory or discontinuous exposure. Interestingly, the frequency of LUF syndrome was 46.2% in patients with inactive inflammatory disease compared to 15% in patients with active disease (P = 0.023). Etoricoxib generated LUF syndrome in 94.2% of the cases with inactive disease versus 28.6% in patients with active disease (P = 0.003). NSAIDs increased the risk of the LUF syndrome, particularly in patients with inactive disease. The selective cyclooxygenase 2 (COX-2) inhibitor etoricoxib was a more potent inductor of LUF syndrome than nonselective COX inhibitors. Continuous periovulatory exposure to NSAIDs should be avoided when planning a pregnancy in patients with rheumatic diseases. Copyright © 2011 by the American College of Rheumatology.

Association of Acetaminophen and Ibuprofen Use With Wheezing in Children With Acute Febrile Illness.

PubMed

Matok, Ilan; Elizur, Arnon; Perlman, Amichai; Ganor, Shani; Levine, Hagai; Kozer, Eran

2017-03-01

Many infants and children receive acetaminophen and/or ibuprofen during febrile illness. Previously, some studies have linked acetaminophen and ibuprofen use to wheezing and exacerbation of asthma symptoms in infants and children. To assess whether acetaminophen or ibuprofen use are associated with wheezing in children presenting to the emergency department (ED) with febrile illness. This was a cross-sectional study of children who presented with fever to the pediatric ED between 2009 and 2013. The data were collected from questionnaires and from the children's medical files. Patients with wheezing in the ED were compared with nonwheezing patients. Associations between medication use and wheezing were assessed using univariate and multivariate analyses. The multivariate analysis adjusted for potential confounding variables (ie, age, atopic dermatitis, allergies, smoking, antibiotics use, etc) via propensity scores. During the study period, 534 children admitted to the ED met our inclusion criteria, of whom 347 (65%) were included in the study. The use of acetaminophen was similar in children diagnosed with wheezing compared with those without wheezing (n = 39, 81.3%, vs n = 229, 82.7%, respectively). Ibuprofen use was significantly lower in children diagnosed with wheezing (n = 22, 52.4%, vs n = 168, 69.4%, respectively). In multivariate analysis, acetaminophen was not associated with a higher rate of wheezing during acute febrile illness (adjusted odds ratio [OR] = 0.76, 95% CI = 0.24- 2.39), whereas ibuprofen was associated with a lower risk of wheezing (adjusted OR = 0.36, 95% CI = 0.13-0.96). Our study suggests that acetaminophen and ibuprofen are not associated with increased risk for wheezing during acute febrile illness.

Non-Steroidal Anti-Inflammatory Drug Use and the Risk of Acute Myocardial Infarction in the General German Population: A Nested Case-Control Study.

PubMed

Thöne, Kathrin; Kollhorst, Bianca; Schink, Tania

2017-09-01

Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been associated with an increased relative risk of acute myocardial infarction (AMI), but the label warnings refer particularly to patients with cardiovascular risk factors. The magnitude of relative AMI risk for patients with and without cardiovascular risk factors varies between studies depending on the drugs and doses studied. The aim of our study was to estimate population-based relative AMI risks for individual and widely used NSAIDs, for a cumulative amount of NSAID use, and for patients with and without a prior history of cardiovascular risk factors. Based on data from the German Pharmacoepidemiological Research Database (GePaRD) of about 17 million insurance members from four statutory health insurance providers, for the years 2004-2009, a nested case-control study was conducted within a cohort of 3,476,931 new NSAID users classified into current, recent, or past users. Up to 100 controls were matched to each case by age, sex, and length of follow-up using risk set sampling. Multivariable conditional logistic regression was applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Duration of NSAID use was calculated by the cumulative amount of dispensed defined daily doses (DDDs), and stratified analyses were conducted for potential effect modifiers. Overall, 17,236 AMI cases were matched to 1,714,006 controls. Elevated relative AMI risks were seen for current users of fixed combinations of diclofenac with misoprostol (OR 1.76, 95% CI 1.26-2.45), indometacin (1.69, 1.22-2.35), ibuprofen (1.54, 1.43-1.65), etoricoxib (1.52, 1.24-1.87), and diclofenac (1.43, 1.34-1.52) compared with past use. A low cumulative NSAID amount was associated with a higher relative AMI risk for ibuprofen, diclofenac, and indometacin. The relative risk associated with current use of diclofenac, fixed combinations of diclofenac with misoprostol, etoricoxib, and ibuprofen was highest in the younger age group

Outcomes studies of the gastrointestinal safety of cyclooxygenase-2 inhibitors.

PubMed

Scheiman, James M

2002-01-01

Short-term endoscopic studies of the highly selective cyclooxygenase-2 (COX-2) inhibitors (coxibs) rofecoxib and celecoxib have shown that these agents are well tolerated and have efficacy equivalent to nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) with fewer adverse effects on the upper gastrointestinal (GI) tract. These studies are limited, however, as the detection of endoscopic lesions is not well correlated with symptomatic ulcers and ulcer complications. Outcomes studies of the GI safety are, therefore, essential to understanding how coxibs are likely to perform in a clinical practice setting. Four large outcomes studies (Vioxx Gastrointestinal Outcomes Research, VIGOR; Assessment of Difference Between Vioxx and Naproxen to Ascertain Gastrointestinal Tolerability and Effectiveness trial, ADVANTAGE; Celecoxib Long-term Arthritis Safety Study, CLASS; and the Successive Celecoxib Efficacy and Safety Studies, SUCCESS) examined the GI safety of rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID (naproxen, ibuprofen, or diclofenac). Reduced risk of upper GI events was seen in patients with multiple risk factors and in patients using low-dose aspirin and corticosteroids concomitantly with a coxib. Results of large outcomes studies provide support for the COX-2 hypothesis and demonstrate the long-term safety and tolerability of coxibs.

Optimisation of cosolvent concentration for topical drug delivery III--influence of lipophilic vehicles on ibuprofen permeation.

PubMed

Watkinson, R M; Guy, R H; Oliveira, G; Hadgraft, J; Lane, M E

2011-01-01

Previously, we have reported the effects of water, ethanol, propylene glycol and various binary and ternary mixtures of these solvents on the permeation of ibuprofen in model membranes and in skin. The present study investigates the influence of lipophilic vehicles on the transport of ibuprofen in silicone membrane and in human skin. The permeation of ibuprofen was measured from mineral oil (MO), Miglyol® 812 (MG) and binary mixtures of MO and MG. The solubility of ibuprofen was 5-fold higher in MG than in MO, however, the permeation of ibuprofen from the pure vehicles and combinations of both was comparable in silicone membrane. Additionally, there were no significant differences in skin permeation for MO and MG vehicles. When the permeation of various hydrophilic and lipophilic vehicles is considered, a trend between flux values for the model membrane and skin is evident (r(2) = 0.71). The findings suggest that silicone membrane may provide information on qualitative trends in skin permeation for vehicles of diverse solubility and partition characteristics. Copyright © 2010 S. Karger AG, Basel.

Dose Responses of Ibuprofen In Vitro on Platelet Aggregation and Coagulation in Human and Pig Blood Samples.

PubMed

Martini, Wenjun Z; Rodriguez, Cassandra M; Deguzman, Rodolfo; Guerra, Jessica B; Martin, Angela K; Pusateri, Anthony E; Cap, Andrew P; Dubick, Michael A

2016-05-01

Ibuprofen is commonly used by warfighters in the deployed environment. This study investigated its dose effects on in vitro coagulation in human and pig blood. Blood samples were collected from 6 normal volunteers and 6 healthy pigs and processed to make platelet-adjusted samples (100 × 10(3)/μL, common transfusion trigger in trauma). Ibuprofen was added to the samples at concentrations of 0 μg/mL (control), the concentration from the highest recommended oral dose (163 μg/mL, 1×), and 2×, 4×, 8×, 10×, 12×, 16×, and 20×. Platelet aggregation by Chrono-Log aggregometer and coagulation by rotational thrombelastogram (Rotem) were assessed at 15 minutes after the addition of ibuprofen. A robust inhibition of ibuprofen on arachidonic acid-induced platelet aggregation was observed at all doses tested in human or pig blood. Collagen-stimulated platelet aggregation was inhibited starting at 1× in human blood and 4× in pig blood. Rotem measurements were similarly compromised in pig and human blood starting at 16×, except clot formation time was prolonged at 1× in human blood (all p < 0.05). Ibuprofen inhibited platelet aggregation at recommended doses, and compromised coagulation at higher doses. Human blood was more sensitive to ibuprofen inhibition. Further effort is needed to investigate ibuprofen dose responses on coagulation in vivo. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

The Photodegradation of Ibuprofen and Dissolved Organic Matter in Lake Superior and St. Louis River Water

PubMed Central

Moynan, Angela B.

2012-01-01

Abstract Ibuprofen can enter bodies of water via waste water treatment. The question was what effect does photodegradation have on ibuprofen and dissolved organic matter (DOM) in Lake Superior (oligiotrophic) and St. Louis (tannic stained) River water? Ibuprofen concentrations of 15,000, 30,000, and 60,000 μg/L were made from lake, river, and distilled water, as well as additional distilled concentrations of 7,500 and 120,000 μg/L. Half of the eighty-four trial cups were placed in an ultraviolet light cabinet and half of the set were placed in a dark cabinet for three days. After the exposure period, a UV-Vis was performed to measure change in molar mass and the summed absorbance of colored dissolved organic matter (CDOM). It appears that ibuprofen decreases in molar mass after exposure to light in distilled and lake water with 15,000 μg/L of ibuprofen. Surprisingly, the molar mass of DOM in river water increases after UV exposure. Possibly, this occurred because the river water has such a high molar mass of DOM and was not filtered. Microbial biomass could also have contributed to this increase. Ibuprofen entering bodies of water via the waste water treatment system appears to be affected by UV light exposure, but in different ways. PMID:23244688

Overview review: Comparative efficacy of oral ibuprofen and paracetamol (acetaminophen) across acute and chronic pain conditions.

PubMed

Moore, R A; Derry, S; Wiffen, P J; Straube, S; Aldington, D J

2015-10-01

Ibuprofen and paracetamol have long been used as analgesics in a range of acute, intermittent and chronic pain conditions. Paracetamol is often the first line analgesic recommended, without consensus about which is the better analgesic. An overview review of systematic reviews and meta-analyses directly compares ibuprofen and paracetamol at standard doses in particular painful conditions, or uses indirect comparisons against placebo. Electronic searches for systematic reviews were sought published since 1995 using outcomes approximating to ≥50% pain intensity reduction. Painful conditions were acute post-operative pain, dysmenorrhoea, tension-type headache (TTH), migraine, osteoarthritis and rheumatoid arthritis, back pain, cancer and paediatric pain. There was no systematic assessment of harm. Sixteen systematic reviews and four individual patient data meta-analyses were included. Ibuprofen was consistently superior to paracetamol at conventional doses in a range of painful conditions. Two direct comparisons favoured ibuprofen (acute pain, osteoarthritis). Three of four indirect comparisons favoured ibuprofen (acute pain, migraine, osteoarthritis); one showed no difference (TTH), although there were methodological problems. In five pain conditions (dysmenorrhoea, paediatric pain, cancer pain, back pain and rheumatoid arthritis), there were limited data on paracetamol and ibuprofen. At standard doses in different painful conditions, ibuprofen was usually superior producing more patients with the degree of pain relief that patients feel worthwhile. Neither of the drugs will be effective for everyone, and both are needed. This overview questions the practice of routinely using paracetamol as a first line analgesic because there is no good evidence for efficacy of paracetamol in many pain conditions. © 2014 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFICC®.

Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial

PubMed Central

James, Nicholas D; Sydes, Matthew R; Mason, Malcolm D; Clarke, Noel W; Anderson, John; Dearnaley, David P; Dwyer, John; Jovic, Gordana; Ritchie, Alastair WS; Russell, J Martin; Sanders, Karen; Thalmann, George N; Bertelli, Gianfilippo; Birtle, Alison J; O'Sullivan, Joe M; Protheroe, Andrew; Sheehan, Denise; Srihari, Narayanan; Parmar, Mahesh KB

2012-01-01

Summary Background Long-term hormone therapy alone is standard care for metastatic or high-risk, non-metastatic prostate cancer. STAMPEDE—an international, open-label, randomised controlled trial—uses a novel multiarm, multistage design to assess whether the early additional use of one or two drugs (docetaxel, zoledronic acid, celecoxib, zoledronic acid and docetaxel, or zoledronic acid and celecoxib) improves survival in men starting first-line, long-term hormone therapy. Here, we report the preplanned, second intermediate analysis comparing hormone therapy plus celecoxib (arm D) with hormone therapy alone (control arm A). Methods Eligible patients were men with newly diagnosed or rapidly relapsing prostate cancer who were starting long-term hormone therapy for the first time. Hormone therapy was given as standard care in all trial arms, with local radiotherapy encouraged for newly diagnosed patients without distant metastasis. Randomisation was done using minimisation with a random element across seven stratification factors. Patients randomly allocated to arm D received celecoxib 400 mg twice daily, given orally, until 1 year or disease progression (including prostate-specific antigen [PSA] failure). The intermediate outcome was failure-free survival (FFS) in three activity stages; the primary outcome was overall survival in a subsequent efficacy stage. Research arms were compared pairwise against the control arm on an intention-to-treat basis. Accrual of further patients was discontinued in any research arm showing safety concerns or insufficient evidence of activity (lack of benefit) compared with the control arm. The minimum targeted activity at the second intermediate activity stage was a hazard ratio (HR) of 0·92. This trial is registered with ClinicalTrials.gov, number NCT00268476, and with Current Controlled Trials, number ISRCTN78818544. Findings 2043 patients were enrolled in the trial from Oct 17, 2005, to Jan 31, 2011, of whom 584 were randomly

Effects of Ibuprofen and Resistance Training on Bone and Muscle: A Randomized Controlled Trial in Older Women.

PubMed

Duff, Whitney R D; Chilibeck, Philip D; Candow, Darren G; Gordon, Julianne J; Mason, Riley S; Taylor-Gjevre, Regina; Nair, Bindu; Szafron, Michael; Baxter-Jones, Adam; Zello, Gordon A; Kontulainen, Saija A

2017-04-01

Resistance training with ibuprofen supplementation may improve musculoskeletal health in postmenopausal women. The study purpose was to determine the efficacy of resistance training and ibuprofen supplementation on bone and muscle properties in postmenopausal women. Participants (n = 90, 65.3 ± 4.9 yr) were randomly assigned to: supervised resistance training or stretching (placebo-exercise) with postexercise ibuprofen (400 mg) or placebo supplementation for 3 d·wk (9 months). Baseline and postintervention measurements included distal and shaft scans of the forearm and lower leg using peripheral quantitative computed tomography. Distal site outcomes included cross-sectional area, content, and density for total and trabecular bone, as well as estimated bone strength in compression. Shaft site outcomes included total bone area; cortical bone area, content, and density; estimated bone strength in torsion; and muscle area and density. Exercise-supplement-time interactions for total bone content at the distal radius (P = 0.009) and cortical density at the radius shaft (P = 0.038) were significant. Resistance training with ibuprofen decreased total bone content (-1.5%) at the distal radius in comparison to the resistance training (0.6%; P = 0.032) and ibuprofen alone (0.5%; P = 0.050). Change in cortical density at the radius shaft differed between the stretching with placebo and ibuprofen supplementation groups (-1.8% vs 1.1%; P = 0.050). Resistance training preserved muscle density in the lower leg more so than stretching (-3.1% vs -5.4%; P = 0.015). Ibuprofen consumed immediately after resistance training had a deleterious effect on bone mineral content at the distal radius, whereas resistance training or ibuprofen supplementation individually prevented bone loss. Resistance training prevented muscle density decline in the lower leg.

Inhibition of RhoA/Rho kinase by ibuprofen exerts cardioprotective effect on isoproterenol induced myocardial infarction in rats.

PubMed

Patel, Prexita; Parikh, Mihir; Shah, Hital; Gandhi, Tejal

2016-11-15

Myocardial infarction (MI) and hypertension are the leading cause of death worldwide so protection of heart is focus of intense research. Rho-kinase, a downstream effector of protein involved in MI and hypertension, is inhibited by ibuprofen. This study aims to elucidate cardioprotective effect of ibuprofen in rats. MI was produced in rats with 85mg/kg isoproterenol (ISO) administered s.c. twice at an interval of 24h. The rats were randomized into six groups: (I) Normal; (II) ISO; (III) ISO + ascorbic acid (250mg/kg p.o.); (IV-VI) ISO + ibuprofen (30, 60 and 90mg/kg p.o). After the completion of the study period of 21 days, cardiac function and biomarkers were assessed. Pre-treatment with ibuprofen (30, 60 and 90mg/kg p.o) ameliorated high BP and left ventricular dysfunction, furthermore it prevented the rise in CKMB, LDH and α-HBDH, suggesting the effect of ibuprofen in maintenance of cell membrane integrity. In addition, it also prevented alteration in the levels of electrolytes, ATPase activity and antioxidant status. Ibuprofen suppressed ISO-induced ROCK-1 mRNA expression and histological changes. Ibuprofen provided cardioprotection in a model of myocardial infarction, by restoring most of the altered physical, physiological, biochemical, haemodynamic parameters, antioxidant status, and histological changes and by inhibiting ROCK-1 mRNA expression. Copyright © 2016 Elsevier B.V. All rights reserved.

Silver-choline chloride modified graphene oxide: Novel nano-bioelectrochemical sensor for celecoxib detection and CCD-RSM model.

PubMed

Parsaee, Zohreh; Karachi, Nima; Abrishamifar, Seyyed Milad; Kahkha, Mohammad Reza Rezaei; Razavi, Razieh

2018-07-01

In this study, silver nanoparticles modified choline chloride functionalized graphene oxide (AgNPs-ChCl-GO) was synthesized using sonochemical method and utilized as a bioelectrochemical sensor for detection of celecoxib (CEL). The characterization studies were ultimately performed in order to acheive a more complete understanding of the morphological and structural features of the AgNPs-ChCl-GO using different techniques including FT-IR, AFM, FE-SEM, EDX, and XRD. AgNPs-ChCl-GO demonstrated a significant improvement in the reduction activity of CEL due to the enhancement in the current response compared to the bare carbon paste electrode (CPE). The optimum experimental conditions, were optimized using central composite design (CCD) methodology. The differential pulse voltammetry (DPVs) showed an expanded linear dynamic ranges of 9.6 × 10 -9 -7.4 × 10 -7  M for celecoxib in Britton-Robinson buffer in pH 5.0 with. LOD (S/N = 3) and LOQ (S/N = 10) were obtained 2.51 × 10 -9  M and 6.58 × 10 -9  M respectively. AgNPs-ChCl-GO-carbon paste electrode exhibited suitable properties and high accuracy determination of celecoxib in the human plasma sample. Copyright © 2018 Elsevier B.V. All rights reserved.

Pain-mediated altered absorption and metabolism of ibuprofen: an explanation for decreased serum enantiomer concentration after dental surgery

PubMed Central

Jamali, Fakhreddin; Kunz-Dober, Cornelia M

1999-01-01

Aims Rapid onset of analgesia is essential in the treatment of acute pain. There is evidence that conditions of stress cause delayed and decreased pain relief from oral analgesic products through impaired absorption. The aim was to determine the effect of surgery for removal of wisdom teeth on the plasma concentration-time profile of ibuprofen enantiomers. Methods Racemic ibuprofen, 200 mg in one group (n=7) and 600 mg in another group (n=7) was administered 1 week before (control) and again after (test) surgical removal of wisdom teeth. Serum concentrations of ibuprofen enantiomers were measured for 6 h. Results During the control phase, S- and R-ibuprofen concentrations were within the suggested therapeutic range. Surgery resulted in a 2 h delay in the mean time to peak concentration, significant decreases in serum ibuprofen concentration following both doses, and a fall to sub-optimal serum concentrations following the 200 mg dose. During the first 2 h after the 200 mg dose, dental extraction resulted in a significant reduction of the area under serum drug concentration (AUC (0, 2 h) mg l−1 h) from 5.6±2.9 to 1.6±1.8 (P<0.01) and from 5.5±3.0 to 2.1±2.0 (P<0.05) for S and R-ibuprofen, respectively. Similar observations were made following the 600 mg dose for AUC (0, 2 h) of S-ibuprofen (from 14.2±6.1 to 7.2±5.5 mg l−1 h, P<0.05) with no significant difference for R-ibuprofen (from 14.4±9.5 to 5.8±7.1). AUC (0, 6 h) was also significantly reduced by surgery. The pattern of stereoselectivity in serum ibuprofen concentration was reversed by surgery such that the S enantiomer was predominant in the control phase but not in the post-surgery phase, which is suggestive of reduced metabolic chiral inversion. Conclusions Surgery for wisdom tooth removal resulted in substantial decreases in the serum concentration of ibuprofen enantiomers and a prolongation in the time to peak concentration. Reduced absorption and altered metabolism are the likely cause of

A Randomized, Multicenter, Phase III Trial to Evaluate the Efficacy and Safety of Polmacoxib Compared with Celecoxib and Placebo for Patients with Osteoarthritis.

PubMed

Lee, Myungchul; Yoo, Juhyung; Kim, Jin Goo; Kyung, Hee-Soo; Bin, Seong-Il; Kang, Seung-Baik; Choi, Choong Hyeok; Moon, Young-Wan; Kim, Young-Mo; Han, Seong Beom; In, Yong; Choi, Chong Hyuk; Kim, Jongoh; Lee, Beom Koo; Cho, Sangsook

2017-12-01

The aim of this study was to evaluate the safety and analgesic efficacy of polmacoxib 2 mg versus placebo in a superiority comparison or versus celecoxib 200 mg in a noninferiority comparison in patients with osteoarthritis (OA). This study was a 6-week, phase III, randomized, double-blind, and parallel-group trial followed by an 18-week, single arm, open-label extension. Of the 441 patients with knee or hip OA screened, 362 were randomized; 324 completed 6 weeks of treatment and 220 completed the extension. Patients were randomized to receive oral polmacoxib 2 mg (n = 146), celecoxib 200 mg (n = 145), or placebo (n = 71) once daily for 6 weeks. During the extension, all participants received open-label polmacoxib 2 mg. The primary endpoint was the change in Western Ontario and McMaster Universities (WOMAC)-pain subscale score from baseline to week 6. Secondary endpoints included WOMAC-OA Index, OA subscales (pain, stiffness, and physical function) and Physician's and Subject's Global Assessments at weeks 3 and 6. Other outcome measures included adverse events (AEs), laboratory tests, vital signs, electrocardiograms, and physical examinations. After 6 weeks, the polmacoxib-placebo treatment difference was -2.5 (95% confidence interval [CI], -4.4 to -0.6; p = 0.011) and the polmacoxib-celecoxib treatment difference was 0.6 (CI, -0.9 to 2.2; p = 0.425). According to Physician's Global Assessments, more subjects were "much improved" at week 3 with polmacoxib than with celecoxib or placebo. Gastrointestinal and general disorder AEs occurred with a greater frequency with polmacoxib or celecoxib than with placebo. Polmacoxib 2 mg was relatively well tolerated and demonstrated efficacy superior to placebo and noninferior to celecoxib after 6 weeks of treatment in patients with OA. The results obtained during the 18-week trial extension with polmacoxib 2 mg were consistent with those observed during the 6-week treatment period, indicating that polmacoxib can be considered

Ibuprofen, paracetamol, and steam for patients with respiratory tract infections in primary care: pragmatic randomised factorial trial.

PubMed

Little, Paul; Moore, Michael; Kelly, Joanne; Williamson, Ian; Leydon, Geraldine; McDermott, Lisa; Mullee, Mark; Stuart, Beth

2013-10-25

To assess strategies for advice on analgesia and steam inhalation for respiratory tract infections. Open pragmatic parallel group factorial randomised controlled trial. Primary care in United Kingdom. Patients aged ≥ 3 with acute respiratory tract infections. 889 patients were randomised with computer generated random numbers in pre-prepared sealed numbered envelopes to components of advice or comparator advice: advice on analgesia (take paracetamol, ibuprofen, or both), dosing of analgesia (take as required v regularly), and steam inhalation (no inhalation v steam inhalation). Primary: mean symptom severity on days 2-4; symptoms rated 0 (no problem) to 7 (as bad as it can be). Secondary: temperature, antibiotic use, reconsultations. Neither advice on dosing nor on steam inhalation was significantly associated with changes in outcomes. Compared with paracetamol, symptom severity was little different with ibuprofen (adjusted difference 0.04, 95% confidence interval -0.11 to 0.19) or the combination of ibuprofen and paracetamol (0.11, -0.04 to 0.26). There was no evidence for selective benefit with ibuprofen among most subgroups defined before analysis (presence of otalgia; previous duration of symptoms; temperature >37.5 °C; severe symptoms), but there was evidence of reduced symptoms severity benefit in the subgroup with chest infections (ibuprofen -0.40, -0.78 to -0.01; combination -0.47; -0.84 to -0.10), equivalent to almost one in two symptoms rated as a slight rather than a moderately bad problem. Children might also benefit from treatment with ibuprofen (ibuprofen: -0.47, -0.76 to -0.18; combination: -0.04, -0.31 to 0.23). Reconsultations with new/unresolved symptoms or complications were documented in 12% of those advised to take paracetamol, 20% of those advised to take ibuprofen (adjusted risk ratio 1.67, 1.12 to 2.38), and 17% of those advised to take the combination (1.49, 0.98 to 2.18). Mild thermal injury with steam was documented for four patients

Enteral feeding during indomethacin and ibuprofen treatment of a patent ductus arteriosus

PubMed Central

Clyman, Ronald; Wickremasinghe, Andrea; Jhaveri, Nami; Hassinger, Denise C.; Attridge, Joshua T.; Sanocka, Ulana; Polin, Richard; Gillam-Krakauer, Maria; Reese, Jeff; Mammel, Mark; Couser, Robert; Mulrooney, Neil; Yanowitz, Toby D.; Derrick, Matthew; Jegatheesan, Priya; Walsh, Michele; Fujii, Alan; Porta, Nicolas; Carey, William A.; Swanson, Jonathan R.

2013-01-01

Objective To test the hypothesis that infants who are just being introduced to enteral feedings will advance to full enteral nutrition at a faster rate if they receive “trophic” (15 ml/kg/day) enteral feedings while receiving indomethacin or ibuprofen treatment for patent ductus arteriosus (PDA). Study design Infants were eligible for the study if they were 231/7 – 306/7 weeks gestation, weighed 401–1250 g at birth, received maximum enteral volumes ≤60 ml/kg/day and were about to be treated with indomethacin or ibuprofen. A standardized “feeding advance regimen” and guidelines for managing feeding intolerance were followed at each site (n=13). Results Infants (n=177; 26.3±1.9 wks (±SD) gestation) were randomized at 6.5±3.9 days to receive “trophic” feeds (“feeding” group, n=81: indomethacin=80%, ibuprofen=20%) or no feeds (“fasting (npo)” group, n=96: indomethacin=75%, ibuprofen=25%) during the drug administration period. Maximum daily enteral volumes prior to study entry were 14±15 ml/kg/day. After drug treatment, infants randomized to the “feeding” arm required fewer days to reach the study’s feeding volume endpoint (120 ml/kg/day). Although the enteral feeding endpoint was reached at an earlier postnatal age, the age at which central venous lines were removed did not differ between the two groups. There were no differences between the two groups in the incidence of infection, necrotizing enterocolitis, spontaneous intestinal perforation or other neonatal morbidities. Conclusion Infants required less time to reach the feeding volume endpoint if they were given “trophic” enteral feedings when they received indomethacin or ibuprofen treatments. PMID:23472765

Development and optimization of the synthesis of new thiazolidin-4-one derivatives of ibuprofen.

PubMed

Vasincu, Ioana; Apotrosoaei, Maria; Panzariu, Andreea; Buron, F; Routier, S; Profire, Lenuta

2014-01-01

Ibuprofen, an important nonsteroidal anti-inflammatory agent, is one of the most prescribed drugs for the treatment of pain and inflammation from various rheumatic diseases, but some side effects can occur on long-term use. The method for synthesis optimization of new derivatives of Ibuprofen with thiazolidin-4-one moiety, with improved pharmacological and toxicological profile. To optimize the derivatization method of free carboxyl group of Ibuprofen (2-(4-isobutylphenyl)propionic acid) the reaction conditions were varied (reagent ratio, catalyst, reaction medium). The most favorable method was proved to be the reaction between ibuprofen hydrazone and mercaptoacetic acid, in excess, at 80-85 degrees C, for 6 h with 96% conversion rate. The synthesis of 2-phenyl-3-[2-(4-(isobutyl)phenyl)-2-methyl]acetamido-thiazolidin-4-one derivative was optimized in view of applying it as a general procedure for the synthesis of other derivatives with related structure. The chemical structure and molecular weight of the synthesized compound were confirmed by spectral methods (IR, 1H NMR, 13C NMR, HR-MS).

Pharmacokinetic and pharmacodynamic interaction between the lipoxygenase inhibitor MK-0591 and the cyclooxygenase inhibitor ibuprofen in man.

PubMed

Depré, M; Van Hecken, A; Verbesselt, R; De Lepeleire, I; Schwartz, J; Porras, A; Larson, P; Lin, C; De Schepper, P J

1998-01-01

Twelve healthy male subjects participated in a double-blind, placebo-controlled, randomized, three-period, crossover study to investigate the safety, tolerability, biochemical activity and pharmacokinetics of ibuprofen, a cyclooxygenase inhibitor and MK-0591, a 5-lipoxygenase inhibitor, given as single entities and in combination. Each subject received for three consecutive 8-day periods, separated by 1 week washout, each of the following treatments: ibuprofen 600 mg three times a day with 125 mg MK-0591 twice a day, ibuprofen 600 mg three times a day with placebo for MK-0591 and MK-0591 125 mg twice a day with placebo for ibuprofen. Cyclooxygenase inhibition was measured by platelet thromboxane (TxB2) generation test, and 5-lipoxygenase inhibition was measured by urinary leukotriene E4 excretion and ex vivo LTB4 generation in calcium-ionophore-stimulated blood. TxB2 suppression on day 8 by ibuprofen was not affected by concomitant treatment with MK-0591. MK-0591 alone had no effect on TxB2 generation. Leukotriene biosynthesis was inhibited by more than 90% by MK-0591 alone and by combined treatment, while ibuprofen alone had no effect. Coadministration appears to affect the pharmacokinetics of MK-0591 (decrease of area under the plasma concentration-vs-time curve [AUC] and maximum plasma concentrations [Cmax]) and of ibuprofen (increase of AUC and half-lives of elimination (t1/2) of the (S)-enantiomer, increase of t1/2 the (R)-enantiomer). Combined treatment had no effect on creatinine clearance nor on the number and intensity of the reported adverse experiences.

Ibuprofen Inhibits Colitis-Induced Overexpression of Tumor-Related Rac1b1

PubMed Central

Matos, Paulo; Kotelevets, Larissa; Goncalves, Vania; Henriques, Andreia; Zerbib, Philippe; Moyer, Mary Pat; Chastre, Eric; Jordan, Peter

2013-01-01

The serrated pathway to colorectal tumor formation involves oncogenic mutations in the BRAF gene, which are sufficient for initiation of hyperplastic growth but not for tumor progression. A previous analysis of colorectal tumors revealed that overexpression of splice variant Rac1b occurs in around 80% of tumors with mutant BRAF and both events proved to cooperate in tumor cell survival. Here, we provide evidence for increased expression of Rac1b in patients with inflamed human colonic mucosa as well as following experimentally induced colitis in mice. The increase of Rac1b in the mouse model was specifically prevented by the nonsteroidal anti-inflammatory drug ibuprofen, which also inhibited Rac1b expression in cultured HT29 colorectal tumor cells through a cyclooxygenase inhibition.independent mechanism. Accordingly, the presence of ibuprofen led to a reduction of HT29 cell survival in vitro and inhibited Rac1b-dependent tumor growth of HT29 xenografts. Together, our results suggest that stromal cues, namely, inflammation, can trigger changes in Rac1b expression in the colon and identify ibuprofen as a highly specific and efficient inhibitor of Rac1b overexpression in colorectal tumors. Our data suggest that the use of ibuprofen may be beneficial in the treatment of patients with serrated colorectal tumors or with inflammatory colon syndromes. PMID:23359345

Effects of ibuprofen, diclofenac and paracetamol on hatch and motor behavior in developing zebrafish (Danio rerio).

PubMed

Xia, Liang; Zheng, Liang; Zhou, Jun Liang

2017-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs) which are widely used as pain relief medicines are causing increasing environmental concern due to their incomplete removal in wastewater treatment plant and potential toxicity on endocrine, kidney and reproduction in teleost fish. This study focused on the effects of widely used ibuprofen, diclofenac and paracetamol on the hatch and motor ability of early-stage zebrafish, by exposing embryos to the target chemicals at 5, 50 and 500 μg/L starting from 6 h postfertilization (hpf). A significant reduction in hatch rate at 55 hpf was caused by both ibuprofen (-63%) and diclofenac (-58%) at 500 μg/L. Exposure to high concentration of ibuprofen significantly decreased the spontaneous movement by 25%, and reduced the free swimming distance, duration and speed under dark condition by 41%, 29% and 30%, respectively. High concentration of diclofenac also caused 23% decrease in spontaneous movement, and reduced the swimming distance as well as active duration by 17% and 13% under light stimulation. In comparison, the exposure to paracetamol did not cause any notable effect. Among neuron related genes tested, the expression of neurog1 was down-regulated from ibuprofen and diclofenac exposure by 19% and 26%, while the expression of neurod1 was up-regulated only by ibuprofen (31%). These findings indicated that ibuprofen and diclofenac significantly affected embryo locomotivity and were potentially neurotoxic, thus posing threats to zebrafish development. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Preparation of ibuprofen/EC-PVP sustained-release composite particles by supercritical CO2 anti-solvent technology].

PubMed

Cai, Jin-Yuan; Huang, De-Chun; Wang, Zhi-Xiang; Dang, Bei-Lei; Wang, Qiu-Ling; Su, Xin-Guang

2012-06-01

Ibuprofen/ethyl-cellulose (EC)-polyvinylpyrrolidone (PVP) sustained-release composite particles were prepared by using supercritical CO2 anti-solvent technology. With drug loading as the main evaluation index, orthogonal experimental design was used to optimize the preparation process of EC-PVP/ibuprofen composite particles. The experiments such as encapsulation efficiency, particle size distribution, electron microscope analysis, infrared spectrum (IR), differential scanning calorimetry (DSC) and in vitro dissolution were used to analyze the optimal process combination. The orthogonal experimental optimization process conditions were set as follows: crystallization temperature 40 degrees C, crystallization pressure 12 MPa, PVP concentration 4 mgmL(-1), and CO2 velocity 3.5 Lmin(-1). Under the optimal conditions, the drug loading and encapsulation efficiency of ibuprofen/EC-PVP composite particles were 12.14% and 52.21%, and the average particle size of the particles was 27.621 microm. IR and DSC analysis showed that PVP might complex with EC. The experiments of in vitro dissolution showed that ibuprofen/EC-PVP composite particles had good sustained-release effect. Experiment results showed that, ibuprofen/EC-PVP sustained-release composite particles can be prepared by supercritical CO2 anti-solvent technology.

Effect of ibuprofen on menstrual blood prostaglandin levels in dysmenorrheic women.

PubMed

Pulkkinen, M O; Csapo, A I

1979-07-01

In a randomized crossover study 15 dysmenorrheic women were treated during two consecutive menstrual period, once with the potent prostaglandin-synthesis inhibitor: ibuprofen and once with an identical looking placebo. Each patient was medicated for 12 hours during the first day of her menstrual flow and was subsequently fitted with a cervical cup for the collection of menstrual blood during three hours. In these samples the concentrations of prostaglandin (PG)F and PGE were measured by radioimmunoassay. The patients receiving placebo had high PGF levels 135 +/- 27 ng/ml (Mean +/- S.E.) which were significnatly reduced by Ibuprofen to 24 +/- 5 ng/ml (P less than 0.001). The PGE concentrations decreased from 5 +/- 1 ng/ml to 2 +/- 1 ng/ml (P less than 0.05). Ibuprofen also reduced the menstrual pain significantly (P less than 0.001). These results substantiate the earlier conclusion that a causal relationship exists between effective treatment with PG-synthesis inhibitors and decrease in menstrual blood PG levels, intrauterine pressure and dysmenorrheic pain.

Controlled Electrostatic Self-Assembly of Ibuprofen-Cationic Dextran Nanoconjugates Prepared by low Energy Green Process - a Novel Delivery Tool for Poorly Soluble Drugs.

PubMed

Abioye, Amos Olusegun; Kola-Mustapha, Adeola

2015-06-01

The direct effect of electrostatic interaction between ibuprofen and cationic dextran on the system-specific physicochemical parameters and intrinsic dissolution characteristics of ibuprofen was evaluated in order to develop drug-polymer nanoconjugate as a delivery strategy for poorly soluble drugs. Amorphous ibuprofen-DEAE dextran (Ddex) nanoconjugate was prepared using a low energy, controlled amphiphile-polyelectrolyte electrostatic self-assembly technique optimized by ibuprofen critical solubility and Ddex charge screening. Physicochemical characteristics of the nanoconjugates were evaluated using FTIR, DSC, TGA, NMR and SEM relative to pure ibuprofen. The in vitro release profiles and mechanism of ibuprofen release were determined using mathematical models including zero and first order kinetics; Higuchi; Hixson-Crowell and Korsmeyer-Peppas. Electrostatic interaction between ibuprofen and Ddex was confirmed with FT-IR, (1)H NMR and (13)C NMR spectroscopy. The broad and diffused DSC peaks of the nanoconjugate as well as the disappearance of ibuprofen melting peak provided evidence for their highly amorphous state. Low concentrations of Ddex up to 1.0 × 10(-6) g/dm(3) enhanced dissolution of ibuprofen to a maximum of 81.32% beyond which retardation occurred steadily. Multiple release mechanisms including diffusion; discrete drug dissolution; anomalous transport and super case II transport were noted. Controlled assembly of ibuprofen and Ddex produced a novel formulation with potential extended drug release dictated by Ddex concentration.

Accelerating the design of molecularly imprinted nanocomposite membranes modified by Au@polyaniline for selective enrichment and separation of ibuprofen

NASA Astrophysics Data System (ADS)

Wu, Xiuling; Wu, Yilin; Dong, Hongjun; Zhao, Juan; Wang, Chen; Zhou, Shi; Lu, Jian; Yan, Yongsheng; Li, He

2018-01-01

A novel system for harvesting molecularly imprinted nanocomposite membranes (MINcMs) with Au-modified polyaniline (Au@polyaniline) nanocomposite structure was developed for selective enrichment and separation of ibuprofen. This unique nanocomposite structure obviously enhanced the adsorption capacity, perm-selectivity performance, and regeneration ability of MINcMs. The as-prepared MINcMs showed outstanding adsorption capacity (22.02 mg g-1) of ibuprofen, which was four times higher than that of non-imprinted nanocomposite membranes (NINcMs). Furthermore, the selectivity factor of MINcMs for ibuprofen reached up to 4.67 and the perm-selectivity factor β was about 8.74, which indicated MINcMs had a good selective separation performance of ibuprofen. We envision that this novel synthesis method will open a new direction to manipulation of molecularly imprinted membrane materials and provide a simple yet convenient way to selective separation of ibuprofen.

Ibuprofen, paracetamol, and steam for patients with respiratory tract infections in primary care: pragmatic randomised factorial trial

PubMed Central

Moore, Michael; Kelly, Joanne; Williamson, Ian; Leydon, Geraldine; McDermott, Lisa; Mullee, Mark; Stuart, Beth

2013-01-01

Objective To assess strategies for advice on analgesia and steam inhalation for respiratory tract infections. Design Open pragmatic parallel group factorial randomised controlled trial. Setting Primary care in United Kingdom. Participants Patients aged ≥3 with acute respiratory tract infections. Intervention 889 patients were randomised with computer generated random numbers in pre-prepared sealed numbered envelopes to components of advice or comparator advice: advice on analgesia (take paracetamol, ibuprofen, or both), dosing of analgesia (take as required v regularly), and steam inhalation (no inhalation v steam inhalation). Outcomes Primary: mean symptom severity on days 2-4; symptoms rated 0 (no problem) to 7 (as bad as it can be). Secondary: temperature, antibiotic use, reconsultations. Results Neither advice on dosing nor on steam inhalation was significantly associated with changes in outcomes. Compared with paracetamol, symptom severity was little different with ibuprofen (adjusted difference 0.04, 95% confidence interval −0.11 to 0.19) or the combination of ibuprofen and paracetamol (0.11, −0.04 to 0.26). There was no evidence for selective benefit with ibuprofen among most subgroups defined before analysis (presence of otalgia; previous duration of symptoms; temperature >37.5°C; severe symptoms), but there was evidence of reduced symptoms severity benefit in the subgroup with chest infections (ibuprofen −0.40, −0.78 to −0.01; combination −0.47; −0.84 to −0.10), equivalent to almost one in two symptoms rated as a slight rather than a moderately bad problem. Children might also benefit from treatment with ibuprofen (ibuprofen: −0.47, −0.76 to −0.18; combination: −0.04, −0.31 to 0.23). Reconsultations with new/unresolved symptoms or complications were documented in 12% of those advised to take paracetamol, 20% of those advised to take ibuprofen (adjusted risk ratio 1.67, 1.12 to 2.38), and 17% of those advised to take the

Grafting of allylimidazole and n-vinylcaprolactam as a thermosensitive polymer onto magnetic nano-particles for the extraction and determination of celecoxib in biological samples.

PubMed

Morovati, Atefeh; Ahmad Panahi, Homayon; Yazdani, Farzaneh

2016-11-20

In this research, a novel method is reported for the surface grafting of n-vinylcaprolactam as a thermosensitive agent and allylimidazole with affinity toward celecoxib onto magnetic nano-particles. The grafted nano-particles were characterized by Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analysis. The surface morphology was studied using Scanning Electron Microscopy. The resulting grafted nano-particles were used for the determination of trace celecoxib in biological human fluids and pharmaceutical samples. The profile of celecoxib uptake by the modified magnetic nano-particles indicated good accessibility of the active sites in the grafted copolymer. It was found that the adsorption behavior could be fitted by the Langmuir adsorption isotherm model. Solid phase extraction for biological fluids such as urine and serum were investigated. In this study, urine extraction recovery of more than 95% was obtained. Copyright © 2016 Elsevier B.V. All rights reserved.

[Relapsing polychondritis. A case report of a patient treated with methotrexate and celecoxib].

PubMed

Cervera Castillo, Hernando; Torres Caballero, Verónica

2005-01-01

Relapsing polychondritis is a rare illness in which the cartilaginous tissues such as auricles, nose, laryngotracheal structures, joints and others, are affected. Customary treatment is based on corticosteroids and traditional antiinflammatory agents including aspirin and indomethacin. We describe a case of relapsing polychondritis in an 82-year-old man with associated diabetes mellitus and special features treated successfully with alternative therapy based on methotrexate and celecoxib.

Efficacy and safety of concurrent chemoradiation with weekly cisplatin ± low-dose celecoxib in locally advanced undifferentiated nasopharyngeal carcinoma: a phase II-III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Razmjou-Ghalaei, Sasan; Shafizad, Amin; Ashouri-Taziani, Yaghoub; Khademi, Bijan; Ahmadloo, Niloofar; Ansari, Mansour; Omidvari, Shapour; Mosalaei, Ahmad; Mosleh-Shirazi, Mohammad Amin

2011-01-01

This is the first study that aimed to determine the efficacy and safety of concurrent chemoradiation with weekly cisplatin ± celecoxib 100 mg twice daily in locally advanced undifferentiated nasopharyngeal carcinoma. Eligible patients had newly diagnosed locally advanced (T3-T4, and/or N2-N3, M0) undifferentiated nasopharyngeal carcinoma, no prior therapy, Karnofsky performance status ≥ 70, and normal organ function. The patients were assigned to receive 7 weeks concurrent chemoradiation (70 Gy) with weekly cisplatin 30 mg/m 2 with either celecoxib 100 mg twice daily, (study group, n = 26) or placebo (control group, n = 27) followed by adjuvant combined chemotherapy with cisplatin 70 mg/m 2 on day 1 plus 5-fluorouracil 750 mg/m 2 /d with 8-h infusion on days 1-3, 3-weekly for 3 cycles. Overall clinical response rate was 100% in both groups. Complete and partial clinical response rates were 64% and 36% in the study group and 44% and 56% in the control group, respectively (P > 0.25). The addition of celecoxib to concurrent chemoradiation was associated with improved 2-year locoregional control rate from 84% to 100% (P = 0.039). The addition of celecoxib 100 mg twice daily to concurrent chemoradiation improved 2-year locoregional control rate.

Impact of a cystic fibrosis transmembrane conductance regulator (CFTR) modulator on high-dose ibuprofen therapy in pediatric cystic fibrosis patients.

PubMed

Bruch, Brittany A; Singh, Sachinkumar B; Ramsey, Laura J; Starner, Timothy D

2018-05-01

This study was undertaken to determine if a clinically relevant drug-drug interaction occurred between ibuprofen and lumacaftor/ivacaftor. Peak ibuprofen plasma concentrations were measured prior to and after lumacaftor/ivacaftor initiation. A Wilcoxon signed rank sum test was used to compare the values. Nine patients were included in the final analysis. Peak ibuprofen plasma concentrations decreased an average of 36.4 mcg/mL after initiation of lumacaftor/ivacaftor with a relative reduction of 41.7%. The average peak plasma concentration was 84.2 mcg/mL (SD = 10.9) prior to lumacaftor/ivacaftor initiation and 47.9 mcg/mL (SD = 16.4) following initiation (P = 0.0039). Peak concentrations occurred at an average of 100 min (SD = 30) and 107 min (SD = 40) prior to and following lumacaftor/ivacaftor initiation, respectively. We suggest a clinically relevant drug-drug interaction exists between ibuprofen and lumacaftor/ivacaftor. Lumacaftor may cause subtherapeutic ibuprofen plasma concentrations due to the induction of CYP enzymes and increased metabolism of ibuprofen. Based on this analysis, we have modified our use of ibuprofen in several patients after evaluation of this drug-drug interaction. © 2018 Wiley Periodicals, Inc.

IL-1beta suppresses the formation of osteoclasts by increasing OPG production via an autocrine mechanism involving celecoxib-related prostaglandins in chondrocytes.

PubMed

Watanabe, Yusuke; Namba, Aki; Aida, Yukiko; Honda, Kazuhiro; Tanaka, Hideki; Suzuki, Naoto; Matsumura, Hideo; Maeno, Masao

2009-01-01

Elevated interleukin (IL)-1 concentrations in synovial fluid have been implicated in joint bone and cartilage destruction. Previously, we showed that IL-1beta stimulated the expression of prostaglandin (PG) receptor EP4 via increased PGE(2) production. However, the effect of IL-1beta on osteoclast formation via chondrocytes is unclear. Therefore, we examined the effect of IL-1beta and/or celecoxib on the expression of macrophage colony-stimulating factor (M-CSF), receptor activator of NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) in human chondrocytes, and the indirect effect of IL-1beta on osteoclast-like cell formation using RAW264.7 cells. OPG and RANKL expression increased with IL-1beta; whereas M-CSF expression decreased. Celecoxib blocked the stimulatory effect of IL-1beta. Conditioned medium from IL-1beta-treated chondrocytes decreased TRAP staining in RAW264.7 cells. These results suggest that IL-1beta suppresses the formation of osteoclast-like cells via increased OPG production and decreased M-CSF production in chondrocytes, and OPG production may increase through an autocrine mechanism involving celecoxib-related PGs.

Comparison of oral and intravenous Ibuprofen for medical closure of patent ductus arteriosus: which one is better?

PubMed

Olukman, Ozgur; Calkavur, Sebnem; Ercan, Gulten; Atlihan, Fusun; Oner, Taliha; Tavli, Vedide; Kultursay, Nilgun

2012-01-01

Intravenous ibuprofen is an expensive drug that is being used currently for treating and preventing patent ductus arteriosus. Although oral ibuprofen is much cheaper, there is limited data published about its safety and efficacy. The aim of this study was to compare two forms of ibuprofen in terms of safety and efficacy in closure of patent ductus arteriosus. This is a single-center retrospective study. Data were collected from patients' files of preterm infants who were hospitalized at the Neonatal Intensive Care Unit of Dr. Behcet Uz Children's Hospital between April 2009 and June 2010. Six hundred sixty infants were evaluated by echocardiography between 24 and 48 postnatal hours. Clinically and hemodynamically significant ductus arteriosus was defined in 66 infants with gestational age less than 32 weeks and birth weight less than 1500 g. Oral or intravenous ibuprofen (loading dose: 10 mg/kg on day 1, followed by maintenance dose: 5 mg/kg on days 2 and 3) was administered. Treatment success was defined as a completely closed duct without reopening on follow-up. Drug-associated renal, gastrointestinal, cerebral, hematological, and metabolic side effects were monitored and compared between treatment groups. Ductal closure rates were 100% and 97.6%, respectively, in the oral and intravenous groups. Hypernatremia was the remarkable side effect in the intravenous group, whereas bronchopulmonary dysplasia and septicemia were prominent in the oral group. No statistically significant difference could be demonstrated between the groups in terms of mortality rates. Oral ibuprofen therapy is as efficacious as intravenous ibuprofen with some concerns about increased sepsis and bronchopulmonary dysplasia incidence. However, comprehensive and large-scale pharmacokinetic studies are required in order to prove this efficacy. On the other hand, intravenous ibuprofen still remains to be the drug of choice for patent ductus arteriosus but only with meticulous control of serum

The pharmacokinetic profile of a novel fixed-dose combination tablet of ibuprofen and paracetamol

PubMed Central

2010-01-01

Background Ibuprofen and paracetamol differ in their mode of action and related therapeutic effects, suggesting that combined administration may offer improved analgesia. Reported here are the results of two studies on the pharmacokinetic properties of a novel ibuprofen (200 mg) and paracetamol (500 mg) fixed-dose combination tablet. Methods Both studies were open-label, randomised studies in healthy volunteers: Study 1 was a four-way crossover, single-dose study; Study 2 was a two-way cross-over, repeat-dose study. Results Pharmacokinetic parameters for ibuprofen and paracetamol were similar for the combination and monotherapy tablets (values falling within the 80% to 125% acceptable bioequivalence range) except for the rate of absorption of paracetamol from the combination (tmax), which was significantly faster compared with monotherapy (median difference 10 minutes; p < 0.05). Mean plasma concentrations of both drugs were higher, earlier, following administration of the combination tablet compared with monotherapy. Mean plasma levels at 10 and 20 minutes were 6.64 μg.mL-1 and 16.81 μg.mL-1, respectively, for ibuprofen from the combination, compared with 0.58 μg.mL-1 and 9.00 μg.mL-1, respectively, for monotherapy. For paracetamol, mean plasma levels at 10 and 20 minutes were 5.43 μg.mL-1 and 14.54 μg.mL-1, respectively, for the combination compared with 0.33 μg.mL-1 and 9.19 μg.mL-1, respectively, for monotherapy. The rate of absorption of both ibuprofen and paracetamol was significantly delayed when the combination tablet was administered in the fed versus fasted state; median delay was 25 minutes for ibuprofen (p > 0.05) and 55 minutes for paracetamol (p < 0.001). The pharmacokinetic parameters were comparable irrespective of whether the combination tablet was given twice or three times daily; systemic exposure was, however, approximately 1.4 times greater for both drugs when given three times daily. Conclusions Administration of ibuprofen and

Multiple-dose pharmacokinetics and safety of an ibuprofen-pseudoephedrine cold suspension in children.

PubMed

Gelotte, Cathy K; Prior, Mary Jane; Pendley, Charles; Zimmerman, Brenda; Lavins, Bernard J

2010-07-01

Two studies were conducted to characterize multiple-dose pharmacokinetics and potential drug interactions of ibuprofen and pseudoephedrine combined in a suspension and to evaluate safety of this combination in children with common cold, flu, or sinusitis. In the pharmacokinetic study, 24 healthy children aged 4-11 years were administered ibuprofen -pseudoephedrine suspension at 7.5 and 1.125 mg/kg, respectively, every 6 hours for 5 doses. Serial blood samples were drawn over 6 hours after final dose for assessment of steady-state pharmacokinetics. In the open-label, multicenter safety study, more than 100 children aged 2-11 years experiencing symptomatic rhinitis were enrolled. Ibuprofen -pseudoephedrine suspension was administered as needed at similar mg/kg doses every 6-8 hours for up to 3 days. Subjects enrolled in the pharmacokinetic study showed no accumulation of either drug; their weight-adjusted clearances were independent of age, and results were comparable with those from previous single-ingredient studies. For ibuprofen, oral clearance (Cl/F) was 77.5 + or - 16.4 mL/kg/h and volume of distribution (Vd/F) was 0.147 + or - 0.037 L/kg. For pseudoephedrine, Cl/F was 12.3 + or - 2.2 mL/kg/min and Vd/F was 2.52 + or - 0.47 L/kg. In the safety study, adverse events were reported for 18.4% of subjects; most were mild to moderate intensity. There was little difference in incidence of adverse events among different age and weight groups. In conclusion, administration of combined ibuprofen and pseudoephedrine in children demonstrated similar pharmacokinetics when compared with reports of the pharmacokinetics for the single-ingredient products, consistent with no apparent drug interactions. The combination suspension was generally well tolerated.

[Efficiency of different celecoxib regimens in patients with active axial spondyloarthritis: Results of the 4-week pilot open-label comparative single-center study 'AIM'].

PubMed

Gaydukova, I Z; Gamayunova, К A; Dorogoykina, K D; Rebrov, A P

To compare the efficiency and safety of two celecoxib regimens in the short-term treatment of patients with axial spondyloarthritis (axSpA). Examinations were made in 40 patients with axSpA (the 2009 ASAS criteria; age, 38.5±12.1 years; 29 (72.5%) men; axSpA duration, 6.67±5.8 years; BASDAI ≥4.0), who were randomly divided into two groups: 1) 20 patients who received celecoxib 400 mg/day for 30 days; 2) 20 patients who took celecoxib 600 mg/day for 7 days, then the drug was continued at a dose of 200 mg/day for 1 month. High-sensitivity C-reactive protein (CRP) was determined; back pain was assessed using a visual analog scale; ASDAS-CRP scores were calculated at baseline (day 0) and on days 8 and 30. On days 0, 8, and 30 of taking celecoxib 400 mg, the back pain scores were 6.0±3.01, 5.06±2.04, and 5.53±2.35; CRP levels, 24.13±21.46; 27.3±29.3%, and 13.1±21.3 mg/l; erythrocyte sedimentation rate (ESR), 15.25±14.36, 11.85±13.6, and 9.5±6.34 mm/h, respectively (p≥0.05 for all differences in all indicators relative to the baseline values). ASDAS was 3.34±1.02 at baseline, 2.74±1.14 on day 8, and 2.18±1.05 on day 30 (p=0.016 and p=0,000 for differences from the baseline values). In the patients using the dose de-escalation of celecoxib, the back pain scores were 4.95±1.6, 4.11±1.0, and 4.89±2.1 at baseline and on days 8 and 30, respectively (p=0.38 and p=0.065 for the differences from the baseline values); the CRP levels were 15.3±12.5, 12.1±10.8, and 7.5±4.5 mg/l, respectively (p=0.3 and p=0.001); ESR, 13.35±7.2, 15.7±11.6, and 15.16±8.9 mm/h (p≥0.05). At baseline and on days 8 and 30, ASDAS was 3.1±0.6, 2.22±0.7, and 3.47±0.56, respectively (p=0.02 and p=0.000). No differences were found in the rate of adverse events. Different regimens using nonsteroidal anti-inflammatory drugs demonstrated their feasibility, efficiency, and safety in AxSpA patients with high disease activity. The continuous use of celecoxib showed a gradual decrease

Simultaneous determination of celecoxib, hydroxycelecoxib, and carboxycelecoxib in human plasma using gradient reversed-phase liquid chromatography with ultraviolet absorbance detection.

PubMed

Störmer, Elke; Bauer, Steffen; Kirchheiner, Julia; Brockmöller, Jürgen; Roots, Ivar

2003-01-05

A new HPLC method for the simultaneous determination of celecoxib, carboxycelecoxib and hydroxycelecoxib in human plasma samples has been developed. Following a solid-phase extraction procedure, the samples were separated by gradient reversed-phase HLPC (C(18)) and quantified using UV detection at 254 nm. The method was linear over the concentration range 10-500 ng/ml. The intra-assay variability for the three analytes ranged from 4.0 to 12.6% and the inter-assay variability from 4.9 to 14.2%. The achieved limits of quantitation (LOQ) of 10 ng/ml for each analyte allowed the determination of the pharmacokinetic parameters of the analytes after administration of 100 mg celecoxib.

Prophylactic Acetaminophen or Ibuprofen Results in Equivalent Acute Mountain Sickness Incidence at High Altitude: A Prospective Randomized Trial.

PubMed

Kanaan, Nicholas C; Peterson, Alicia L; Pun, Matiram; Holck, Peter S; Starling, Jennifer; Basyal, Bikash; Freeman, Thomas F; Gehner, Jessica R; Keyes, Linda; Levin, Dana R; O'Leary, Catherine J; Stuart, Katherine E; Thapa, Ghan B; Tiwari, Aditya; Velgersdyk, Jared L; Zafren, Ken; Basnyat, Buddha

2017-06-01

Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness (AMS), yet the proposed anti-inflammatory mechanism remains unconfirmed. Acetaminophen and ibuprofen were tested for AMS prevention. We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen's mechanism of possible symptom reduction by predominantly mediating nociception in the brain. A double-blind, randomized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS. A total of 332 non-Nepali participants were recruited at Pheriche (4371 m) and Dingboche (4410 m) on the Everest Base Camp trek. The participants were randomized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche (4940 m), where they were reassessed. The primary outcome was AMS incidence measured by the Lake Louise Questionnaire score. Data from 225 participants who met inclusion criteria were analyzed. Twenty-five participants (22.1%) in the acetaminophen group and 18 (16.1%) in the ibuprofen group developed AMS (P = .235). The combined AMS incidence was 19.1% (43 participants), 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location, suggesting that both interventions reduced the incidence of AMS. We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence. This suggests that AMS prevention may be multifactorial, affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception. Additional study is needed. Copyright © 2017 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Displacement chromatography on cyclodextrin silicas. IV. Separation of the enantiomers of ibuprofen.

PubMed

Farkas, G; Irgens, L H; Quintero, G; Beeson, M D; al-Saeed, A; Vigh, G

1993-08-13

A displacement chromatographic method has been developed for the preparative separation of the enantiomers of ibuprofen using a beta-cyclodextrin silica stationary phase. The retention behavior of ibuprofen was studied in detail: the log k' vs. polar organic modifier concentration, the log k' vs. pH, the log k' vs. buffer concentration and the log k' vs. 1/T relationships; also, the alpha vs. polar organic modifier concentration, the alpha vs. pH, the alpha vs. buffer concentration and the log alpha vs. 1/T relationships have been determined in order to find the carrier solution composition which results in maximum chiral selectivity and sufficient, but not excessive solute retention (1 < k' < 30). 4-tert.-Butylcyclohexanol, a structurally similar but more retained compound than ibuprofen, was selected as displacer for the separation. Even with an alpha value as small as 1.08, good preparative chiral separations were observed both in the displacement mode and in the overloaded elution mode, up to a sample load of 0.5 mg.

Comparison of intravenous ibuprofen and acetaminophen for postoperative multimodal pain management in bariatric surgery: A randomized controlled trial.

PubMed

Erdogan Kayhan, Gulay; Sanli, Mukadder; Ozgul, Ulku; Kirteke, Ramazan; Yologlu, Saim

2018-06-20

Multimodal analgesic strategies are recommended to decrease opioid requirements and opioid-induced respiratory complications in patients undergoing laparoscopic bariatric surgery. Recent studies have demonstrated that intravenous ibuprofen decreases opioid consumption compared with placebo. The primary aim of this study was to compare the effect of intravenous ibuprofen and intravenous acetaminophen on opioid consumption. We also aimed to compare postoperative pain levels and side effects of the drugs. Randomized, double-blinded study. University hospital. Eighty patients, aged 18-65 years, (ASA physical status II-III) undergoing laparoscopic sleeve gastrectomy or laparoscopic Roux-en-Y gastric bypass surgery were included in this study. Patients were randomized to receive 800 mg ibuprofen or 1 g acetaminophen intravenously every 6 h for the first 24 h following surgery; in addition, patient-controlled analgesia with morphine was administered. Postoperative morphine consumption in the first 24 h, visual analog scale (VAS) pain scores at rest and with movement, and opioid related side effects were assessed. In addition, time to passage of flatus, surgical complications, lengths of intensive care unit and hospital stay, and laboratory parameters were recorded. The mean morphine consumption was 23.94 ± 13.89 mg in iv ibuprofen group and 30.23 ± 13.76 mg in the acetaminophen group [mean difference: -6.28 (95% CI, -12.70, 0.12); P = 0.055]. The use of intravenous ibuprofen was associated with reduction in pain at rest (AUC, 1- to 24-h, P < 0.001 and 12- to 24-h, P = 0.021) and pain with movement (AUC, 1-24, 6-24, and 12-24 h, P < 0.001). Intravenous ibuprofen was well tolerated with no serious side effects except dizziness. Intravenous ibuprofen did not significantly reduce opioid consumption compared to intravenous acetaminophen; however, it reduced the severity of pain. Intravenous ibuprofen may be a good alternative to

Crystal engineering of ibuprofen compounds: From molecule to crystal structure to morphology prediction by computational simulation and experimental study

NASA Astrophysics Data System (ADS)

Zhang, Min; Liang, Zuozhong; Wu, Fei; Chen, Jian-Feng; Xue, Chunyu; Zhao, Hong

2017-06-01

We selected the crystal structures of ibuprofen with seven common space groups (Cc, P21/c, P212121, P21, Pbca, Pna21, and Pbcn), which was generated from ibuprofen molecule by molecular simulation. The predicted crystal structures of ibuprofen with space group P21/c has the lowest total energy and the largest density, which is nearly indistinguishable with experimental result. In addition, the XRD patterns for predicted crystal structure are highly consistent with recrystallization from solvent of ibuprofen. That indicates that the simulation can accurately predict the crystal structure of ibuprofen from the molecule. Furthermore, based on this crystal structure, we predicted the crystal habit in vacuum using the attachment energy (AE) method and considered solvent effects in a systematic way using the modified attachment energy (MAE) model. The simulation can accurately construct a complete process from molecule to crystal structure to morphology prediction. Experimentally, we observed crystal morphologies in four different polarity solvents compounds (ethanol, acetonitrile, ethyl acetate, and toluene). We found that the aspect ratio decreases of crystal habits in this ibuprofen system were found to vary with increasing solvent relative polarity. Besides, the modified crystal morphologies are in good agreement with the observed experimental morphologies. Finally, this work may guide computer-aided design of the desirable crystal morphology.

Up-regulation of p53 and mitochondrial signaling pathway in apoptosis by a combination of COX-2 inhibitor, Celecoxib and Dolastatin 15, a marine mollusk linear peptide in experimental colon carcinogenesis.

PubMed

Piplani, Honit; Vaish, Vivek; Rana, Chandan; Sanyal, Sankar N

2013-11-01

Programmed cell death, also known as apoptosis, is an active process occurring in eukaryotic cells and it depends on various sets of pro and anti-apoptotic proteins. Chemoprevention of colorectal cancer can be achieved by inducing apoptosis using synthetic compound, Celecoxib and natural peptide, Dolastatin 15 in an effective manner. But the apoptotic signaling by these two drugs remain unclear. The present study was thus focused on the role of Bcl2 family of proteins and their interplay with p53 in rats during the chemoprevention by these two drugs. After treatment for 6 wk with 1, 2-dimethylhydrazine (DMH), animals showed a marked occurrence of multiple plaque lesions. However, a simultaneous treatment with Celecoxib and Dolastatin 15 decreases such number to a significant level. DMH treatment also decreases the number of apoptotic cells in the colonic enterocytes which were corrected to the normal level by Celecoxib and Dolastatin 15. An increased expression of Bcl2 while other proteins like Bax, Apaf-1, cyt c, and caspases in the apoptotic pathway, and the tumor suppressor proteins, p53 and p21 get down-regulated after DMH treatment which were reverted back to normal with Celecoxib and Dolastatin 15. Also, cells having high mitochondrial membrane potential had been seen to increase to significant levels which were reduced after the administration of these anti-inflammatory drugs. In silico molecular docking studies also showed that Dolastatin 15 and Celecoxib may bind to the active site pocket of Bcl2 , thus revealing the direct target of Dolastatin 15 and Celecoxib apart from binding to COX-2. © 2012 Wiley Periodicals, Inc.

Celecoxib-Induced Self-Assembly of Smart Albumin-Doxorubicin Conjugate for Enhanced Cancer Therapy.

PubMed

Shi, Leilei; Xu, Li; Wu, Chenwei; Xue, Bai; Jin, Xin; Yang, Jiapei; Zhu, Xinyuan

2018-03-14

Recent years have witnessed the great contributions that drug combination therapy has made for enhanced cancer therapy. However, because of the complicated pharmacokinetics of combined drug formulations, the majority of combination strategies show severe adverse effects at high dosage and poor biodistribution in vivo. To overcome these deficiencies and achieve enhanced cancer therapy, we put forward a method to construct a smart albumin-based nanoplatform, denoted as K237-HSA-DC, for codelivery of cyclooxygenase-2 (COX-2) inhibitor (celecoxib) and chemotherapeutic agent (doxorubicin, DOX). Both in vitro and in vivo studies indicate that K237-HSA-DC exhibits the best therapeutic efficacy on tumor cells compared with all the other formulations. Moreover, K237-HSA-DC shows fewer side effects on normal organs in contrast to other formulations. To understand the reasons behind the improved drug efficacy in depth, we performed a cell metabonomics-based mechanism study and found that celecoxib could enhance the inhibitory effect of DOX on the transport of glucose into cells and then lead to subsequent significant energy metabolism inhibition. Considering the above-mentioned advantages of K237-HSA-DC, we believe the smart albumin-based nanoplatform can serve as a promising drug delivery system for enhanced cancer therapy.

Synthesis and Pharmacological Evaluation of New Chemical Entities from Ibuprofen as Novel Analgesic Candidates.

PubMed

Ahmadi, A; Naderi, N; Daniali, M; Kazemi, S; Aazami, S; Alizadeh, N; Nahri-Niknafs, B

2015-09-01

Non-steroidal anti-inflammatory drugs (NSAIDs) are the first choice of drugs that are normally used for the treatment of pain and inflammation. Ibuprofen (I) and its analogues as the most widely used NSAIDs have been synthesized in recent years. In an effort to establish new candidates with improved analgesic properties, derivatives (II-VII) with substituted aromatic as well as aliphatic moieties were synthesized in this experiment and evaluated in formalin test with rats. The results were compared to ibuprofen and control groups. Findings indicated that derivatives with new alkylphenyl rings (VI and VII) had some similar or more analgesic activities relative to the control and ibuprofen groups, respectively; which could be justified as to more alkyl and phenyl groups instead of p-isobutylphenyl moiety in I. © Georg Thieme Verlag KG Stuttgart · New York.

Synthesis of Ibuprofen in the Introductory Organic Laboratory

ERIC Educational Resources Information Center

Kjonaas, Richard A.; Williams, Peggy E.; Counce, David A.; Crawley, Lindsey R.

2011-01-01

A method for the synthesis of ibuprofen in introductory organic chemistry laboratory courses is reported. This experiment requires two 3-h lab sessions. All of the reactions and techniques are a standard part of any introductory organic chemistry course. In the first lab session, students reduce p-isobutylacetophenone to an alcohol and then…

The effects and safety of dexibuprofen compared with ibuprofen in febrile children caused by upper respiratory tract infection

PubMed Central

Yoon, Jong Seo; Jeong, Dae-Chul; Oh, Jae-Won; Lee, Keun Young; Lee, Hyun Seung; Koh, Young Yull; Kim, Jin Tack; Kang, Jin Han; Lee, Joon Sung

2008-01-01

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECTThe analgesic and anti-inflammatory efficacy of dexibuprofen compared with ibuprofen in adults with osteoarthritis, rheumatoid arthritis and dental pain. WHAT THIS STUDY ADDSDexibuprofen is as effective and tolerable as ibuprofen, and a dose of 5 mg kg−1 of dexibuprofen would be sufficient to control fever caused by upper respiratory tract infection in children. AIM To evaluate the antipyretic efficacy and tolerability of dexibuprofen compared with ibuprofen in children with fever caused by upper respiratory tract infection (URTI). METHODS The study population consisted of children aged 6 months to 14 years. At the time of visit to the hospital, the children had fever; the cause of fever was determined to be URTI by a paediatrician based on history taking and physical examination. The study was a multicentre, randomized, double-blind, controlled parallel group, comparative, Phase 3 clinical trial, conducted at three hospitals. By using a computer-based random assignment program, the subjects were allocated to the following three groups: 5 mg kg−1 dexibuprofen group, 7 mg kg−1 dexibuprofen group, and 10 mg kg−1 ibuprofen group. RESULTS In the clinical trial of the antipyretic action of dexibuprofen in patients with fever caused by URTI, there was no statistically significant difference in maximal decrease of temperature and mean time to become apyrexial among the 5 mg kg−1 dexibuprofen, 7 mg kg−1 dexibuprofen and 10 mg kg−1 ibuprofen groups (P > 0.05). There also was no significant difference in adverse drug reaction (P > 0.05). CONCLUSIONS Dexibuprofen is as effective and tolerable as ibuprofen. A dose of 5 mg kg−1 and 7 mg kg−1 dexibuprofen in place of 10 mg kg−1 ibuprofen would be sufficient to control fever caused by URTI in children. PMID:19032727

Ibuprofen with acetaminophen for postoperative pain control following tonsillectomy does not increase emergency department utilization.

PubMed

Bedwell, Joshua R; Pierce, Matthew; Levy, Michelle; Shah, Rahul K

2014-12-01

To compare the performance of ibuprofen vs codeine for postoperative pain management after tonsillectomy as measured by need for emergency department (ED) treatment for pain and/or dehydration. Retrospective case series with chart review. Tertiary children's hospital. Consecutive series of patients who underwent tonsillectomy with or without adenoidectomy at a tertiary children's hospital. Patients were categorized based on the type of postoperative pain management (acetaminophen with codeine vs acetaminophen and ibuprofen). The main outcome measure was the proportion of patients requiring ED visits or inpatient admissions for inadequate pain control or dehydration. Secondary measures included antibiotic use, postoperative hemorrhage, need for return to the operating room, vomiting, and oral diet tolerance. Patients in the ibuprofen/acetaminophen group were younger than those in the codeine/acetaminophen group (6.2 vs 8.1 years, P < .05). Patients in the codeine/acetaminophen group were more likely to use antibiotics in the postoperative period (50.3% vs 5.9%, P < .05). The proportion of patients requiring ED visits or inpatient admission for dehydration was not significantly different between the groups (5.1% for codeine, 2.7% for ibuprofen, P = .12). Multivariable analysis controlling for age and antibiotic use showed no difference in ED visits or admission for dehydration (P = .09). There was no difference between the groups for any of the secondary measures. Ibuprofen with acetaminophen represents a safe and acceptable analgesic alternative to codeine and acetaminophen in patients undergoing pediatric tonsillectomy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

[Use of over-the-counter drugs containing ibuprofen in self-medication].

PubMed

Macesková, B

2001-05-01

Ibuprofen (MO1AE01) is a suitable means for self-medication with regard to its relatively wide spectrum of indication, good tolerance, and safety. In the Czech Republic, OTC preparations containing ibuprofen represent frequently used medicaments. The paper examines solid divided dosage forms for oral administration. A survey based on questionnaires reveals in what indications and according to what dosing schemes the purchased preparations are used, and the paper evaluates possible risks. Strengthening of the role of the pharmacist as the provider of information on drugs, keeping patients' drug records in pharmacies, and deepening of the mutual cooperation of the physician and pharmacist would contribute to increase the safety of the use of the preparations under study.

Controlled release of ibuprofen by meso-macroporous silica

NASA Astrophysics Data System (ADS)

Santamaría, E.; Maestro, A.; Porras, M.; Gutiérrez, J. M.; González, C.

2014-02-01

Structured meso-macroporous silica was successfully synthesized from an O/W emulsion using decane as a dispersed phase. Sodium silicate solution, which acts as a silica source and a poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (EO19PO39EO19) denoted as P84 was used in order to stabilize the emulsion and as a mesopore template. The materials obtained were characterized through transmission electron microscopy (TEM), scanning electron microscopy (SEM), small-angle X-ray diffraction scattering (SAXS) and nitrogen adsorption-desorption isotherms. Ibuprofen (IBU) was selected as the model drug and loaded into ordered meso-macroporous materials. The effect of the materials’ properties on IBU drug loading and release was studied. The results showed that the loading of IBU increases as the macropore presence in the material is increased. The IBU adsorption process followed the Langmuir adsorption isotherm. A two-step release process, consisting of an initial fast release and then a slower release was observed. Macropores enhanced the adsorption capacity of the material; this was probably due to the fact that they allowed the drug to access internal pores. When only mesopores were present, ibuprofen was probably adsorbed on the mesopores close to the surface. Moreover, the more macropore present in the material, the slower the release behaviour observed, as the ibuprofen adsorbed in the internal pores had to diffuse along the macropore channels up to the surface of the material. The material obtained from a highly concentrated emulsion was functionalized with amino groups using two methods, the post-grafting mechanism and the co-condensation mechanism. Both routes improve IBU adsorption in the material and show good behaviour as a controlled drug delivery system.

Vapour-phase method in the synthesis of polymer-ibuprofen sodium-silica gel composites.

PubMed

Kierys, Agnieszka; Krasucka, Patrycja; Grochowicz, Marta

2017-11-01

The study discusses the synthesis of polymer-silica composites comprising water soluble drug (ibuprofen sodium, IBS). The polymers selected for this study were poly(TRIM) and poly(HEMA- co -TRIM) produced in the form of permanently porous beads via the suspension-emulsion polymerization method. The acid and base set ternary composites were prepared by the saturation of the solid dispersions of drug (poly(TRIM)-IBS and/or poly(HEMA- co -TRIM)-IBS) with TEOS, and followed by their exposition to the vapour mixture of water and ammonia, or water and hydrochloric acid, at autogenous pressure. The conducted analyses reveal that the internal structure and total porosity of the resulting composites strongly depend on the catalyst which was used for silica precursor gelation. The parameters characterizing the porosity of both of the acid set composites are much lower than the parameters of the base set composites. Moreover, the basic catalyst supplied in the vapour phase does not affect the ibuprofen sodium molecules, whereas the acid one causes transformation of the ibuprofen sodium into the sodium chloride and a derivative of propanoic acid, which is poorly water soluble. The release profiles of ibuprofen sodium from composites demonstrate that there are differences in the rate and efficiency of drug desorption from them. They are mainly affected by the chemical character of the polymeric carrier but are also associated with the restricted swelling of the composites in the buffer solution after precipitation of silica gel.

Efficacy of preoperative ibuprofen and meloxicam on the success rate of inferior alveolar nerve block for teeth with irreversible pulpitis.

PubMed

Shantiaee, Yazdan; Javaheri, Sahar; Movahhedian, Amir; Eslami, Sarah; Dianat, Omid

2017-04-01

The purpose of this study was to determine whether premedication with ibuprofen or meloxicam increases the success rate of anaesthesia in teeth with irreversible pulpitis. In this parallel, double-blind clinical trial, 92 patients diagnosed with irreversible pulpitis were randomly divided into four groups of 23 patients. The first group (the no-premedication group) received no premedication, the second group (the meloxicam group) received 7.5 mg of meloxicam, the third group (the ibuprofen group) received 600 mg of ibuprofen, and the fourth group (the placebo group) received placebo 1 hour before intervention. Before taking the medication, electrical pulp testing (EPT) and the Heft-Parker visual analogue scale (VAS) were used to evaluate sensitivity and pain at baseline. Then, local anaesthesia was injected, and after 15 minutes, EPT was used again to evaluate tooth sensitivity. The pain during access preparation was also recorded using the Heft-Parker VAS. Ninety-two patients were analysed. The success rates of local anaesthesia were 21.7%, 34.8%, 78.3% and 73.9% in the no-premedication, placebo, ibuprofen and meloxicam groups, respectively, according to the EPT values. Considering the Heft-Parker VAS values, no premedication gave a 21.7% success rate, placebo gave a 34.8% success rate, ibuprofen gave an 82.6% success rate and meloxicam gave a 65.2% success rate. The ibuprofen and meloxicam groups showed significantly better results than the placebo and no-premedication groups (P < 0.001). However, the difference between meloxicam and ibuprofen groups was not significant. Premedication with meloxicam and ibuprofen significantly increased the success rates of inferior alveolar nerve block anaesthesia for teeth with irreversible pulpitis; however, neither drug provided profound anaesthesia. © 2016 FDI World Dental Federation.

Ibuprofen for the treatment of patent ductus arteriosus in preterm and/or low birth weight infants.

PubMed

Ohlsson, A; Walia, R; Shah, S

2008-01-23

A patent ductus arteriosus (PDA) complicates the clinical course of preterm infants, increasing their risks of developing chronic lung disease (CLD), necrotizing enterocolitis (NEC), and intraventricular hemorrhage (IVH). Indomethacin is used as standard therapy to close a PDA, but is associated with reduced blood flow to the brain, kidneys and gastrointestinal tract. Ibuprofen, another cyclo-oxygenase inhibitor, may be as effective as indomethacin, with fewer side effects. To determine the effectiveness and safety of ibuprofen compared to placebo or no intervention for closing a PDA in preterm and/or low birth weight infants. To determine the effectiveness and safety of ibuprofen compared to other cyclo-oxygenase inhibitors (including indomethacin, mefenamic acid) for closing a PDA in preterm and/or low birth weight infants. Randomized or quasi-randomized controlled trials (RCTs) comparing ibuprofen to placebo or indomethacin or mefenamic acid for therapy of PDA were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2007), MEDLINE (1996 - August 2007), CINAHL (1982 - August 2007), EMBASE (1980 - August 2007), reference lists of published RCTs and abstracts from the Pediatric Academic Societies and the European Society for Pediatric Research meetings published in Pediatric Research (1991 - April 2005) or on their website (to August 2007). No language restrictions were applied. 1) DESIGN: Randomized or quasi-randomized controlled trials2) POPULATION: Preterm (< 37 weeks gestational age) or low birth weight infants (< 2500 g) with a clinically or echocardiographically diagnosed PDA3) INTERVENTION: Administration of ibuprofen (orally or intravenously) for the closure of PDA4) OUTCOMES: At least one of the following outcomes were reported: failure to close a PDA, mortality, surgical ductal ligation, intraventricular haemorrhage (IVH), periventricular leukomalacia (PVL), NEC, decreased urine output

Comparative Effect of Cinnamon and Ibuprofen for Treatment of Primary Dysmenorrhea: A Randomized Double-Blind Clinical Trial

PubMed Central

Jaafarpour, Molouk; Hatefi, Masoud; Khajavikhan, Javaher

2015-01-01

Background and Aims Primary dysmenorrheal has a negative impact on women's quality of life. The purpose of this study was to compare the effect of Cinnamon and Ibuprofen for treatment of primary dysmenorrheal in a sample of Iranian female college students from Ilam University of Medical Sciences (western Iran). Materials and Methods In a randomized, double-blind trial, out of 114, control group received placebo (empty capsules contain starch, TDS, n= 38) a test group received Ibuprofen (capsule containing 400mg Ibuprofen, TDS, n=38), or another test group received Cinnamon (capsule containing 420 mg Cinnamon, TDS, n= 38) in 24 h. To determine severity of pain, we used the VAS scale. Pain intensity and duration of pain were monitored in the group during first 72 h of cycle. Results The mean pain severity score and mean duration of pain in Ibuprofen and Cinnamon were less than placebo group respectively (p< 0.001). Of 4 hours after the intervention there were no statistically significant differences between the Cinnamon and placebo group (p> 0.05). Of eight hours after the intervention, the mean pain severity in the cinnamon group was significantly lower than placebo group (p< 0.001). At various time intervals the mean pain severity in the Ibuprofen group were significantly less than Cinnamon and placebo groups (p< 0.001). Conclusion Cinnamon compared with placebo significantly reduced the severity and duration of pain during menstruation, but this effect was lower compared with Ibuprofen. Cinnamon can be regarded as a safe and effective treatment for primary dysmenorrhea. More researches are recommended to study the efficacy of Cinnamon on reducing menstrual bleeding. PMID:26023601

Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment

PubMed Central

Markworth, James F.; Vella, Luke; Lingard, Benjamin S.; Tull, Dedreia L.; Rupasinghe, Thusitha W.; Sinclair, Andrew J.; Maddipati, Krishna Rao

2013-01-01

Classical proinflammatory eicosanoids, and more recently discovered lipid mediators with anti-inflammatory and proresolving bioactivity, exert a complex role in the initiation, control, and resolution of inflammation. Using a targeted lipidomics approach, we investigated circulating lipid mediator responses to resistance exercise and treatment with the NSAID ibuprofen. Human subjects undertook a single bout of unaccustomed resistance exercise (80% of one repetition maximum) following oral ingestion of ibuprofen (400 mg) or placebo control. Venous blood was collected during early recovery (0–3 h and 24 h postexercise), and serum lipid mediator composition was analyzed by LC-MS-based targeted lipidomics. Postexercise recovery was characterized by elevated levels of cyclooxygenase (COX)-1 and 2-derived prostanoids (TXB2, PGE2, PGD2, PGF2α, and PGI2), lipooxygenase (5-LOX, 12-LOX, and 15-LOX)-derived hydroxyeicosatetraenoic acids (HETEs), and leukotrienes (e.g., LTB4), and epoxygenase (CYP)-derived epoxy/dihydroxy eicosatrienoic acids (EpETrEs/DiHETrEs). Additionally, we detected elevated levels of bioactive lipid mediators with anti-inflammatory and proresolving properties, including arachidonic acid-derived lipoxins (LXA4 and LXB4), and the EPA (E-series) and DHA (D-series)-derived resolvins (RvD1 and RvE1), and protectins (PD1 isomer 10S, 17S-diHDoHE). Ibuprofen treatment blocked exercise-induced increases in COX-1 and COX-2-derived prostanoids but also resulted in off-target reductions in leukotriene biosynthesis, and a diminished proresolving lipid mediator response. CYP pathway product metabolism was also altered by ibuprofen treatment, as indicated by elevated postexercise serum 5,6-DiHETrE and 8,9-DiHETrE only in those receiving ibuprofen. These findings characterize the blood inflammatory lipid mediator response to unaccustomed resistance exercise in humans and show that acute proinflammatory signals are mechanistically linked to the induction of a

Formulation and Evaluation of a Novel Matrix-Type Orally Disintegrating Ibuprofen Tablet

PubMed Central

Tayebi, Hoda; Mortazavi, Seyed Alireza

2011-01-01

Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation. PMID:24250378

Synthesis and hydrolytic behaviour of glycerol-1,2-diibuprofenate-3-nitrate, a putative pro-drug of ibuprofen and glycerol-1-nitrate.

PubMed

Ingram, M J; Moynihan, H A; Powell, M W; Rostron, C

2001-03-01

Nitroxylated derivatives of non-steroidal anti-inflammatory drugs appear to offer protection against the gastrotoxicity normally associated with non-steroidal anti-inflammatory drugs, ostensibly via local production of nitric oxide. A diester of ibuprofen and glycerol-1-mononitrate has been prepared via the condensation of ibuprofen with 3-bromopropan-1,2-diol, followed by silver-(I)-nitrate-mediated nitroxylation. The release of ibuprofen from this diester has been studied in a simulated gastric fluid model with direct analysis by reverse-phase HPLC, using an acetonitrile-water (80%:20%) mobile phase containing trifluoroacetic acid (0.005%). n-Propyl ibuprofen was found to undergo pH-dependent hydrolysis, ranging from negligible hydrolysis at pH 5 to 52% hydrolysis at pH 3, over a 2-h period in this model. The ibuprofen-glycerol mononitrate diester was subjected to the most vigorous model hydrolytic conditions and was found to undergo 50 % hydrolysis during the study period. This study shows that pro-drugs of ibuprofen and glycerol mononitrate can be obtained, and can undergo degradation to the parent drugs under conditions simulating those likely to be encountered in the stomach.

Formulation and delivery strategies of ibuprofen: challenges and opportunities.

PubMed

Irvine, Jake; Afrose, Afrina; Islam, Nazrul

2018-02-01

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose.

Celecoxib aggravates cardiac apoptosis in L-NAME-induced pressure overload model in rats: Immunohistochemical determination of cardiac caspase-3, Mcl-1, Bax and Bcl-2.

PubMed

Mosaad, Sarah M; Zaitone, Sawsan A; Ibrahim, Abdelazim; El-Baz, Amani A; Abo-Elmatty, Dina M; Moustafa, Yasser M

2017-06-25

The mechanism of celecoxib cardiovascular adverse events was earlier investigated; yet in-depth investigations are needed to assess the involvement of its pro-apoptotic effect throughout this process. An in-vivo chronic rat model of pressure overload employing Nʷ-nitro-l-arginine methyl ester (L-NAME) was tested at different time intervals to ensure the occurrence of persistent myocardial apoptosis along with pressure overload. Seven groups of male Wistar rats were assigned as (i) distilled water; (ii-iv) L-NAME (60 mg/kg) for 6, 12 or 16 weeks; (v-vii) L-NAME [16 weeks] + celecoxib (25, 50 or 100 mg/kg), from week 13 to week 16. Treatment with L-NAME for 6, 12 or 16 weeks increased systolic blood pressure, serum level of creatine kinase-MB and lactate dehydrogenase. Further, it induced cardiac hypertrophy, detected in terms of greater heart weight index and cardiomyocyte cross-sectional area and produced interstitial and perivascular fibrosis. Moreover, administration of L-NAME increased cardiac immunostaining for activated caspase-3 and Bax/Bcl-2 ratio whereas; immunostaining for Mcl-1 was decreased. Administration of celecoxib (25, 50 or 100 mg/kg) aggravated the L-NAME-induced toxicity. The work results shed the light on the putative pro-apoptotic effect of celecoxib at a risk state of pressure overload comparable to the clinical condition of essential hypertension. Copyright © 2017 Elsevier B.V. All rights reserved.

Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens

PubMed Central

Annamanedi, Madhavi; Varma, Gajapati Y. N.; Anuradha, K.; Kalle, Arunasree M.

2017-01-01

Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections. PMID:28533769

Celecoxib Enhances the Efficacy of Low-Dose Antibiotic Treatment against Polymicrobial Sepsis in Mice and Clinical Isolates of ESKAPE Pathogens.

PubMed

Annamanedi, Madhavi; Varma, Gajapati Y N; Anuradha, K; Kalle, Arunasree M

2017-01-01

Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens ( Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa , and Enterobacter species). The in vivo results clearly demonstrated a significant reduction in the bacterial load in different organs and in the inflammatory markers such as COX-2 and NF-κB via activation of SIRT1 in mice treated with imipenem, a choice of antibiotic for polymicrobial sepsis treatment. Combinatorial treatment of ampicillin and celecoxib was effective on clinical isolates of ESKAPE pathogens, 45% of tested clinical isolates showed more than 50% reduction in the colony forming units when compared to ampicillin alone. In conclusion, this non-traditional treatment strategy might be effective in clinic to reduce the dose of antibiotic to treat drug-resistant bacterial infections.

In vivo assessment of parenteral formulations of oligo(3-hydroxybutyric Acid) conjugates with the model compound Ibuprofen.

PubMed

Stasiak, Pawel; Sznitowska, Malgorzata; Ehrhardt, Carsten; Luczyk-Juzwa, Maria; Grieb, Pawel

2010-12-01

Polymer-drug conjugates have gained significant attention as pro-drugs releasing an active substance as a result of enzymatic hydrolysis in physiological environment. In this study, a conjugate of 3-hydroxybutyric acid oligomers with a carboxylic acid group-bearing model drug (ibuprofen) was evaluated in vivo as a potential pro-drug for parenteral administration. Two different formulations, an oily solution and an o/w emulsion were prepared and administered intramuscularly (IM) to rabbits in a dose corresponding to 40 mg of ibuprofen/kilogramme. The concentration of ibuprofen in blood plasma was analysed by HPLC, following solid-phase extraction and using indometacin as internal standard (detection limit, 0.05 microg/ml). No significant differences in the pharmacokinetic parameters (C (max), T (max), AUC) were observed between the two tested formulations of the 3-hydroxybutyric acid conjugate. In comparison to the non-conjugated drug in oily solution, the relative bioavailability of ibuprofen conjugates from oily solution, and o/w emulsion was reduced to 17% and 10%, respectively. The 3-hydroxybutyric acid formulations released the active substance over a significantly extended period of time with ibuprofen still being detectable 24 h post-injection, whereas the free compound was almost completely eliminated as early as 6 h after administration. The conjugates remained in a muscle tissue for a prolonged time and can hence be considered as sustained release systems for carboxylic acid derivatives.

Ibuprofen Potentiates the In Vivo Antifungal Activity of Fluconazole against Candida albicans Murine Infection

PubMed Central

Miranda, Isabel M.; Silva-Dias, Ana; Silva, Ana P.; Rodrigues, Acácio G.; Pina-Vaz, Cidália

2015-01-01

Candida albicans is the most prevalent cause of fungemia worldwide. Its ability to develop resistance in patients receiving azole antifungal therapy is well documented. In a murine model of systemic infection, we show that ibuprofen potentiates fluconazole antifungal activity against a fluconazole-resistant strain, drastically reducing the fungal burden and morbidity. The therapeutic combination of fluconazole with ibuprofen may constitute a new approach for the management of antifungal therapeutics to reverse the resistance conferred by efflux pump overexpression. PMID:25845879

Agglomeration of Celecoxib by Quasi Emulsion Solvent Diffusion Method: Effect of Stabilizer.

PubMed

Maghsoodi, Maryam; Nokhodchi, Ali

2016-12-01

Purpose: The quasi-emulsion solvent diffusion (QESD) has evolved into an effective technique to manufacture agglomerates of API crystals. Although, the proposed technique showed benefits, such as cost effectiveness, that is considerably sensitive to the choice of a stabilizer, which agonizes from a absence of systemic understanding in this field. In the present study, the combination of different solvents and stabilizers were compared to investigate any connections between the solvents and stabilizers. Methods: Agglomerates of celecoxib were prepared by QESD method using four different stabilizers (Tween 80, HPMC, PVP and SLS) and three different solvents (methyl acetate, ethyl acetate and isopropyl acetate). The solid state of obtained particles was investigated by differential scanning calorimetry (DSC) and Fourier transform infrared (FT-IR) spectroscopy. The agglomerated were also evaluated in term of production yield, distribution of particles and dissolution behavior. Results: The results showed that the effectiveness of stabilizer in terms of particle size and particle size distribution is specific to each solvent candidate. A stabilizer with a lower HLB value is preferred which actually increased its effectiveness with the solvent candidates with higher lipophilicity. HPMC appeared to be the most versatile stabilizer because it showed a better stabilizing effect compared to other stabilizers in all solvents used. Conclusion: This study demonstrated that the efficiency of stabilizers in forming the celecoxib agglomerates by QESD was influenced by the HLB of the stabilizer and lipophilicity of the solvents.

Ibuprofen and paracetamol for pain relief during medical abortion: a double-blind randomized controlled study.

PubMed

Livshits, Anna; Machtinger, Ronit; David, Liat Ben; Spira, Maya; Moshe-Zahav, Aliza; Seidman, Daniel S

2009-05-01

To determine the efficacy of a nonsteroidal anti-inflammatory drug vs. paracetamol in pain relief during medical abortion and to evaluate whether nonsteroidal anti-inflammatory drugs interfere with the action of misoprostol. A prospective double-blind controlled study. University-affiliated tertiary hospital. One hundred twenty women who underwent first-trimester termination of pregnancy. Patients received 600 mg mifepristone orally, followed by 400 microg of oral misoprostol 2 days later. They were randomized to receive ibuprofen or paracetamol when pain relief was necessary. Patients completed a questionnaire about side effects and pain score and returned for an ultrasound follow-up examination 10-14 days after medical abortion. Success rates, as defined by no surgical intervention, and pain scores were assessed. Ibuprofen was found to be statistically significantly more effective for pain relief after medical abortion compared with paracetamol. There was no difference in the failure rate of medical abortion, and the frequency of surgical intervention was slightly higher in the group that received paracetamol (16.3% vs. 8.5%). Ibuprofen was found to be more effective than paracetamol for pain reduction during medical abortion. A history of surgical or medical abortion was predictive for high pain scores. Despite its anti-prostaglandin effects, ibuprofen use did not interfere with the action of misoprostol.

The Resolution of Ibuprofen, 2-(4'-Isobutylphenyl) Propionic Acid

ERIC Educational Resources Information Center

McCullagh, James V.

2008-01-01

In this experiment the over-the-counter pain reliever ibuprofen is resolved using (S)-(-)-[alpha]-phenethylamine as the resolving agent. This procedure has several key advantages over previous resolution experiments. First, it involves the resolution of a well-known medicinal compound of commercial importance. Second, the resolution process is…

Design and evaluation of mucoadhesive microemulsion for neuroprotective effect of ibuprofen following intranasal route in the MPTP mice model.

PubMed

Mandal, Surjyanarayan; Mandal, Snigdha Das; Chuttani, Krishna; Sawant, Krutika K; Subudhi, Bharat Bhushan

2016-08-01

The present study is to investigate the neuroprotective effect of ibuprofen by intranasal administration of mucoadhesive microemulsion (MMEI) against inflammation-mediated by dopaminergic neurodegeneration in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease (PD). Ibuprofen-loaded polycarbophil-based MMEI was developed by using response surface methodology (RSM). Ibuprofen with dose of 2.86 mg/kg/day was administered intranasally to male C57BL/6 mice for two consecutive weeks which were pre-treated with four intraperitoneal injections of MPTP (20 mg/kg of body weight) at 2 h intervals. Immunohistochemistry was performed. Optimal MMEI was stable and non-ciliotoxic with 66.29 ± 4.15 nm as average globule size and -20.9 ± 3.98 mV as zeta potential. PDI value and transmission electron microscopy result showed the narrow globule size distribution of MMEI. The result showed that all three independent variables had a significant effect (p < 0.05) on the responses. Rota-rod and open-field test findings revealed the significant improvement in motor performance and gross behavioral activity of the mice. The results from in vivo study and immunohistochemistry showed that nasal administration of Ibuprofen significantly reduced the MPTP-mediated dopamine depletion. Furthermore TH neurons count in the substantia nigra and the density of striatal dopaminergic nerve terminals were found to be significant higher for ibuprofen treated groups. Findings of the investigation revealed that Ibuprofen through developed MMEI was shown to protect neurons against MPTP-induced injury in the Substantia nigra pars compacta (SNpc) and striatum and hence, could be a promising approach for brain targeting of Ibuprofen through intranasal route to treat PD.

Real-time monitoring of the mechanism of ibuprofen-cationic dextran crystanule formation using crystallization process informatics system (CryPRINS).

PubMed

Abioye, Amos Olusegun; Chi, George Tangyie; Simone, Elena; Nagy, Zoltan

2016-07-25

One step aqueous melt-crystallization and in situ granulation was utilized to produce ibuprofen-cationic dextran [diethylaminoethyl dextran (Ddex)] conjugate crystanules without the use of surfactants or organic solvents. This study investigates the mechanism of in situ granulation-induced crystanule formation using ibuprofen (Ibu) and Ddex. Laboratory scale batch aqueous crystallization system containing in situ monitoring probes for particle vision measurement (PVM), UV-vis measurement and focused beam reflectance measurements (FBRM) was adapted using pre-defined formulation and process parameters. Pure ibuprofen showed nucleation domain between 25 and 64°C, producing minicrystals with onset of melting at 76°C and enthalpy of fusion (ΔH) of 26.22kJ/mol. On the other hand Ibu-Ddex crystanules showed heterogeneous nucleation which produced spherical core-shell structure. PVM images suggest that internalization of ibuprofen in Ddex corona occurred during the melting phase (before nucleation) which inhibited crystal growth inside the Ddex corona. The remarkable decrease in ΔH of the crystanules from 26.22 to 11.96kJ/mol and the presence of broad overlapping DSC thermogram suggests formation of ibuprofen-Ddex complex and crystalline-amorphous transformation. However Raman and FTIR spectra did not show any significant chemical interaction between ibuprofen and Ddex. A significant increase in dissolution efficiency from 45 to 81% within 24h and reduced burst release provide evidence for potential application of crystanules in controlled drug delivery systems. It was evident that in situ granulation of ibuprofen inhibited the aqueous crystallization process. It was concluded that in situ granulation-aqueous crystallization technique is a novel unit operation with potential application in continuous pharmaceutical processing. Copyright © 2016 Elsevier B.V. All rights reserved.

[Recurrent aseptic meningitis secondary to taking ibuprofen and ketorolac].

PubMed

Cano Vargas-Machuca, E; Mondéjar-Marín, B; Navarro-Muñoz, S; Pérez-Molina, I; Garrido-Robres, J A; Alvarez-Tejerina, A

Aseptic meningitis is a process that is characterised by an inflammatory reaction of the meninges that is not due to any infectious agent. Its aetiology is varied and is most frequently caused by rheumatologic and/or autoimmune processes, chemical or medication-induced meningitis, the most notable drugs involved being antibiotics and non-steroidal anti-inflammatory drugs (NSAI). We report the case of a 70-year-old male, with no relevant history, who was admitted to hospital five times over a period of 16 months because of acute meningitis with polymorphonuclear pleocytosis, high protein levels in cerebrospinal fluid and normal glucose in cerebrospinal fluid. No evidence of an infectious causation, chemical meningitis, carcinomatosis or autoimmune disease was found and the patient was diagnosed with recurrent aseptic meningitis. It was found that the patient had taken ibuprofen or ketorolac on several occasions, a few hours before the appearance of symptoms. These episodes were quickly resolved after withdrawal of this medication. A number of NSAI have been reported as inducers of aseptic meningitis, one of the most notable being ibuprofen. We report the case of a patient who, as a consequence of taking ibuprofen and ketorolac, presented episodes of recurrent aseptic meningitis. To our knowledge this side effect of ketorolac has not been reported before. Its clinical features are impossible to differentiate from those of infectious meningitis. Diagnosis is reached by exclusion and a careful pharmacological study, including over-the-counter drugs like some of the NSAI, must be performed in patients with this condition, since it is a problem that can easily be solved by withdrawing the drug that causes it.

Celecoxib prevents colitis associated colon carcinogenesis: an upregulation of apoptosis.

PubMed

Setia, Shruti; Nehru, Bimla; Sanyal, Sankar N

2014-12-01

Uncontrolled cell proliferation and suppressed apoptosis are the critical events transforming a normal cell to a cancerous one wherein the inflammatory microenvironment supports this oncogenic transformation. The process of colon carcinogenesis may be aggravated in chronic inflammatory conditions such as ulcerative colitis where non-steroidal anti-inflammatory drugs (NSAIDs) may effectively prevent the cellular and molecular events. Western blots and immunofluorescent analysis of DNA mismatch repair enzymes, cell cycle regulators and pro- and anti-apoptotic proteins were performed in dextran sulfate sodium (DSS)-induced ulcerative colitis and 1,2-dimethyl benz(a)anthracene (DMH)-induced colon cancer. Also, apoptotic studies were done in isolated colonocytes using fluorescent staining and in paraffin sections using TUNEL assay. An upregulation of cell cycle regulators: cyclin D1/cdk4 and cyclin E/cdk2 and anti-apoptotic Bcl-2, along with the suppression of DNA repair enzymes: MLH1 and MSH2; tumour suppressors: p53, p21and Rb and pro-apoptotic proteins: Bax and Bad were observed in the DSS, DMH and DSS+DMH groups. Proliferating cell nuclear antigen (PCNA) was also overexpressed in these groups. The ultimate executioner of the apoptotic pathway; caspase-3, was suppressed in these groups. Apoptotic studies in colonocytes and paraffin sections revealed suppressed apoptosis in these groups. These effects were corrected with the administration of a second generation NSAID, celecoxib along with the treatment of DSS and DMH. The chemopreventive action of celecoxib in colitis mediated colon carcinogenesis may include the regulation of DNA mismatch repair enzymes, cell cycle check points, cell proliferation and apoptosis. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Exisulind in combination with celecoxib modulates epidermal growth factor receptor, cyclooxygenase-2, and cyclin D1 against prostate carcinogenesis: in vivo evidence.

PubMed

Narayanan, Bhagavathi A; Reddy, Bandaru S; Bosland, Maarten C; Nargi, Dominick; Horton, Lori; Randolph, Carla; Narayanan, Narayanan K

2007-10-01

Nonsteroidal anti-inflammatory drugs mediate anticancer effects by modulating cyclooxygenase-2 (COX-2)-dependent and/or COX-2-independent mechanism(s); however, the toxicity issue is a concern with single agents at higher doses. In this study, we determined the combined effect of celecoxib, a COX-2 inhibitor, along with exisulind (sulindac sulfone/Aptosyn) at low doses in prostate cancer. We used a sequential regimen of N-methyl-N-nitrosourea + testosterone to induce prostate cancer in Wistar-Unilever rats. Following carcinogen treatment, celecoxib and exisulind individually and their combination at low doses were given in NIH-07 diet for 52 weeks. We determined the incidence of prostatic intraepithelial neoplasia, adenocarcinomas, rate of tumor cell proliferation, and apoptosis. Immunohistochemical and Western blot analysis were done to determine COX-2, epidermal growth factor receptor (EGFR), Akt, androgen receptor, and cyclin D1 expression. Serum prostaglandin E2 and tumor necrosis factor-alpha levels were determined using enzyme immunoassay/ELISA assays. The rats that received celecoxib in combination with exisulind at low doses showed a significant decrease in prostatic intraepithelial neoplasia and adenocarcinomas as well as an enhanced rate of apoptosis. An overall decrease in COX-2, EGFR, Akt, androgen receptor, and cyclin D1 expression was found associated with tumor growth inhibition. Reduced serum levels of COX-2 protein, prostaglandin E2, and tumor necrosis factor-alpha indicated anti-inflammatory effects. A strong inhibition of total and phosphorylated form of EGFR (Tyr(992) and Tyr(845)) and Akt (Ser(473)) was significant in rats given with these agents in combination. In this study, we show for the first time that the combination of celecoxib with exisulind at low doses could prevent prostate carcinogenesis by altering key molecular events.

BCL-2 and BCL-XL expression are down-regulated in benign prostate hyperplasia nodules and not affected by finasteride and/or celecoxib

PubMed Central

Li, Feng; Pascal, Laura E; Zhou, Jianhua; Zhou, Yibin; Wang, Ke; Parwani, Anil V; Dhir, Rajiv; Guo, Peng; He, Dalin; Nelson, Joel B; Wang, Zhou

2018-01-01

The mechanisms involved in the development of benign prostatic hyperplasia (BPH) are poorly understood. One potential mechanism involved in BPH pathogenesis may involve altered expression of genes related to apoptosis and proliferation because reduced cell death and increased proliferation are thought to contribute to prostatic enlargement. This study examined the expression of B-cell lymphoma 2 (BCL-2) and B-cell lymphoma-extra large (BCL-XL), two important anti-apoptosis factors that are also capable of inhibiting cell proliferation via accelerated G1 arrest or delayed G1/S transition, using immunostaining in simple prostatectomy BPH specimens from patients naïve to androgen manipulation. Since androgens and inflammation are thought to play important roles in BPH pathogenesis, we tested the effect of inhibiting 5a-reductase and/or COX-2 on the expression of BCL-2 and BCL-XL in BPH specimens from prostate cancer patients with BPH. These patients had no prior use of chronic NSAIDs and/or 5a-reductase inhibitors and were treated with celecoxib, finasteride, celecoxib plus finasteride or no treatment for 28 consecutive days prior to surgery. In all specimens, BCL-2 and BCL-XL staining was evident in both luminal and basal epithelial cells, with more intense staining in basal cells. Both luminal and basal cells exhibited decreased BCL-2 and BCL-XL staining in BPH nodules compared to the surrounding normal prostatic tissues. In prostate cancer patients with BPH, celecoxib and/or finasteride did not affect the expression of BCL-2 and BCL-XL in luminal or basal cells in BPH nodules and normal adjacent tissues. These results suggest that BCL-2 and BCL-XL may act as anti-proliferative factors in BPH pathogenesis, and the effect of celecoxib and/or finasteride on BPH is unlikely mediated through modulating BCL-2 and BCL-XL signaling. PMID:29531971

Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer

PubMed Central

Khan, O A; Blann, A D; Payne, M J; Middleton, M R; Protheroe, A S; Talbot, D C; Taylor, M; Han, C; Patil, M; Harris, A L

2011-01-01

Background: Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial. Methods: Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured. Results: Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers. Conclusion: This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium. PMID:21587257

Continuous low-dose cyclophosphamide and methotrexate combined with celecoxib for patients with advanced cancer.

PubMed

Khan, O A; Blann, A D; Payne, M J; Middleton, M R; Protheroe, A S; Talbot, D C; Taylor, M; Kirichek, O; Han, C; Patil, M; Harris, A L

2011-06-07

Combined therapy of metronomic cyclophosphamide, methotrexate and high-dose celecoxib targeting angiogenesis was used in a phase II trial. Patients with advanced cancer received oral cyclophosphamide 50 mg o.d., celecoxib 400 mg b.d. and methotrexate 2.5 mg b.d. for two consecutive days each week. Response was determined every 8 weeks; toxicity was evaluated according to CTC version 2.0. Plasma markers of inflammation, coagulation and angiogenesis were measured. Sixty-seven of 69 patients were evaluable for response. Twenty-three patients had stable disease (SD) after 8 weeks, but there were no objective responses to therapy. Median time to progression was 57 days. There was a low incidence of toxicities. Among plasma markers, levels of tissue factor were higher in the SD group of patients at baseline, and levels of both angiopoietin-1 and matrix metalloproteinase-9 increased in the progressive disease group only. There were no changes in other plasma markers. This metronomic approach has negligible activity in advanced cancer albeit with minimal toxicity. Analysis of plasma markers indicates minimal effects on endothelium in this trial. These data for this particular regimen do not support basic tenets of metronomic chemotherapy, such as the ability to overcome resistant tumours by targeting the endothelium.

Use of decimal assay for additivity to demonstrate synergy in pair combinations of econazole, nikkomycin Z, and ibuprofen against Candida albicans in vitro.

PubMed Central

Tariq, V N; Scott, E M; McCain, N E

1995-01-01

Interactions between six compounds (econazole, miconazole, amphotericin B, nystatin, nikkomycin Z, and ibuprofen) were investigated for their antifungal activities against Candida albicans by using pair combinations in an in vitro decimal assay for additivity based on disk diffusion. Additive interactions were observed between miconazole and econazole, amphotericin B and nystatin, and amphotericin B and ibuprofen, while an antagonistic interaction was observed between econazole and amphotericin B. Synergistic interactions were recorded for the combinations of econazole and ibuprofen, econazole and nikkomycin Z, and ibuprofen and nikkomycin Z. PMID:8592989

Timing of ibuprofen use and bone mineral density adaptations to exercise training.

PubMed

Kohrt, Wendy M; Barry, Daniel W; Van Pelt, Rachael E; Jankowski, Catherine M; Wolfe, Pamela; Schwartz, Robert S

2010-06-01

Prostaglandins (PGs) are essential signaling factors in bone mechanotransduction. In animals, inhibition of the enzyme responsible for PG synthesis (cyclooxygenase) by nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the bone-formation response to loading when administered before, but not immediately after, loading. The aim of this proof-of-concept study was to determine whether the timing of NSAID use influences bone mineral density (BMD) adaptations to exercise in humans. Healthy premenopausal women (n = 73) aged 21 to 40 years completed a supervised 9-month weight-bearing exercise training program. They were randomized to take (1) ibuprofen (400 mg) before exercise, placebo after (IBUP/PLAC), (2) placebo before, ibuprofen after (PLAC/IBUP), or (3) placebo before and after (PLAC/PLAC) exercise. Relative changes in hip and lumbar spine BMD from before to after exercise training were assessed using a Hologic Delphi-W dual-energy X-ray absorptiometry (DXA) instrument. Because this was the first study to evaluate whether ibuprofen use affects skeletal adaptations to exercise, only women who were compliant with exercise were included in the primary analyses (IBUP/PLAC, n = 17; PLAC/PLAC, n = 23; and PLAC/IBUP, n = 14). There was a significant effect of drug treatment, adjusted for baseline BMD, on the BMD response to exercise for regions of the hip (total, p < .001; neck, p = .026; trochanter, p = .040; shaft, p = .019) but not the spine (p = .242). The largest increases in BMD occurred in the group that took ibuprofen after exercise. Total-hip BMD changes averaged -0.2% +/- 1.3%, 0.4% +/- 1.8%, and 2.1% +/- 1.7% in the IBUP/PLAC, PLAC/PLAC, and PLAC/IBUP groups, respectively. This preliminary study suggests that taking NSAIDs after exercise enhances the adaptive response of BMD to exercise, whereas taking NSAIDs before may impair the adaptive response. (c) 2010 American Society for Bone and Mineral Research.

Effect of Secondary Equilibria on the Adsorption of Ibuprofen Enantiomers on a Chiral Stationary Phase with a Grafted Antibiotic Eremomycin

NASA Astrophysics Data System (ADS)

Reshetova, E. N.; Asnin, L. D.; Kachmarsky, K.

2018-02-01

The chromatographic separation of ibuprofen enantiomers on a Nautilus-E chiral stationary phase with a grafted eremomycin antibiotic at high column loading is accompanied by distortion of the shape of chromatographic peaks. A model is proposed to explain this phenomenon. A number of factors are considered in the model: the ionization of ibuprofen in the mobile phase, the pH change in the mass transfer zone caused by ionization, and competitive adsorption involving buffer components. Simulations performed using this model within the theory of nonequilibrium chromatography allow the shape of chromatograms for large amounts of S- and R-ibuprofen samples to be predicted. The adsorption mechanism is found to be mainly ion-exchange. The contribution from the molecular adsorption of ibuprofen to the total retention is shown to be several percent.

The shortened infusion time of intravenous ibuprofen, part 2: a multicenter, open-label, surgical surveillance trial to evaluate safety.

PubMed

Gan, Tong J; Candiotti, Keith; Turan, Alparslan; Buvanendran, Asokumar; Philip, Beverly K; Viscusi, Eugene R; Soghomonyan, Suren; Bergese, Sergio D

2015-02-01

The literature and clinical data support the use of intravenous (IV) infusions of ibuprofen to control pain and reduce the opioid requirements associated with surgical pain. According to current guidelines, IV ibuprofen can be administered via a slow IV infusion performed during a 30-minute period. Although recent studies indicate that more rapid infusions may yield additional benefits for patients, the safety of such an approach needs further evaluation. The main purpose of this study was to determine the safety of single and multiple doses of IV ibuprofen (800 mg) administered over 5 to 10 minutes at the induction of anesthesia and after the surgical procedure for the treatment of postoperative pain. This was a Phase IV, multicenter, open-label, clinical surveillance study. It was conducted at 21 hospitals in the United States, and 300 adult hospitalized patients undergoing surgery were enrolled. The exclusion criteria for the study were: inadequate IV access; hypersensitivity to any component of IV ibuprofen, aspirin, or related products; and any active, clinically significant bleeding. Also excluded were patients who had taken NSAIDs <6 hours before administration of IV ibuprofen; pregnant or breastfeeding female patients; and patients in the perioperative period of coronary artery bypass graft surgery. Patients received 800 mg of IV ibuprofen administered over 5 to 10 minutes preoperatively. Vital signs, adverse events, and pain scores were assessed. Approximately 22% (65 of 300) of patients reported adverse events (serious and nonserious). The most common adverse event was infusion site pain (34 of 300 [11%]). No deaths were reported. Nine subjects reported serious adverse events, 8 of which occurred during the first 6 hours. All serious events reported were judged unrelated to ibuprofen. Of the 300 total patients, 2 (0.67%) discontinued the study drug due to an adverse event (1 patient discontinued the study because of infusion site pain, and 1 patient

Devitrification of amorphous celecoxib.

PubMed

Gupta, Piyush; Bansal, Arvind K

2005-09-30

The purpose of this research was to analyze the devitrification of amorphous celecoxib (CEL) in the presence of different stressors (temperature, pressure, and/or humidity) encountered during processing of solid dosage forms. Amorphous CEL was prepared in situ in the analytical instruments, as well as in laboratory, by quench-cooling of melt process, and analyzed by dynamic mechanical thermal analysis, differential scanning calorimetry, microscopy, and Fourier-transform infrared spectroscopy. Amorphous CEL prepared in situ in the analytical instruments was resistant to crystallization under the influence of temperature and/or pressure, because of its protection from the external environment during preparation. These samples exhibited structural relaxation during annealing at 25 degrees C/0% relative humidity (RH) for 16 hours. Generation of amorphous CEL in the laboratory resulted in partially crystalline samples, because of exposure to environmental temperature and humidity, resulting in incomplete vitrification. Subjection to thermal stress favored crystallization of amorphous CEL into metastable polymorphic forms, which were not obtained by solvent recrystallization approach. Temperature and humidity were identified as the major factors promoting devitrification of amorphous CEL, leading to loss of solubility advantage. Exposure to International Conference on Harmonization-specified accelerated stability storage conditions (40 degrees C/75% RH) resulted in complete devitrification of amorphous CEL within 15 days. The phase-transformation process of amorphous CEL along the temperature scale was examined visually, as well as spectrally. This propensity for devitrification of amorphous CEL seemed to depend on the strength of differential molecular interactions between the amorphous and crystalline form.

An ibuprofen-antagonized plasmin inhibitor released by human endothelial cells.

PubMed

Rockwell, W B; Ehrlich, H P

1991-02-01

Serum-free culture medium harvested from endothelial cell monolayer cultures derived from human scars and dermis was examined for inhibition of fibrinolysis using a fibrin plate assay. Human cultured fibroblasts and smooth muscle cells did not produce any detectable inhibitory activity. The inhibitor is spontaneously released from the cultured endothelial cells over time. In the fibrin plate assay of plasmin-induced fibrinolysis, one nonsteroidal antiinflammatory (NSAI) drug, ibuprofen, was demonstrated to antagonize the inhibition of fibrinolysis. The antagonistic activity of ibuprofen appears unrelated to its NSAI drug activity because other NSAI drugs such as indomethacin and tolmetin have minimal antagonistic activity. Heating the cultured endothelial cells to 42 degrees C stimulates greater release of the inhibitor in a shorter period of time. This plasmin inhibitor, which is produced by endothelial cells, may contribute to postburn vascular occlusion, leading to secondary progressive necrosis in burn-traumatized patients.

Efficacy and safety of additional 200-mg dose of celecoxib in adult patients with postoperative pain following extraction of impacted third mandibular molar: a multicenter, randomized, double-blind, placebo-controlled, phase II study in Japan.

PubMed

Saito, Ken'ichi; Kaneko, Akihiro; Machii, Katsuyuki; Ohta, Hiroyoshi; Ohkura, Masayuki; Suzuki, Makoto

2012-02-01

Although third mandibular molar extraction is a widely used and validated model of acute pain for evaluating analgesic efficacy, a large proportion of patients experience moderate or severe pain following this procedure and require analgesia. Current treatment options have been associated with safety concerns and alternative therapies are sought. Our aim was to assess the efficacy and safety of an additional 200-mg dose of celecoxib, administered 5 to 12 hours after an initial 400-mg dose of the drug for the treatment of moderate or severe acute pain following extraction of an impacted third mandibular molar. This was a multicenter, randomized, double-blind, placebo-controlled, Phase II study. Patients experiencing moderate or severe pain within 1 to 2 hours following extraction of an impacted third mandibular molar received an initial 400-mg dose of celecoxib. Patients requiring additional analgesia were subsequently randomized to receive either an additional 200-mg dose of celecoxib or placebo 5 to 12 hours after the initial dose. The study was designed and conducted by Pfizer Inc. for approval of celecoxib in Japan for the indication of acute pain. The primary end point was the patient's impression of efficacy (4-category global evaluation scale). Secondary efficacy end points included pain intensity on a 4-category pain intensity scale, pain intensity on a 100-mm visual analog scale (VAS), and the pain intensity difference (100-mm VAS). In an exploratory analysis, use of rescue medication was evaluated. Primary and secondary end points were analyzed using the full analysis set. Assessment of the safety profile included a physical examination, measurement of pulse rate and blood pressure, standard 12-lead ECG, and laboratory tests. A total of 69 patients (celecoxib, 42/64 [65.6%]; placebo, 27/58 [46.6%]) received the additional dose of study medication; all completed the study without the need for rescue medication. A significantly higher proportion of patients

Antipyretic effect of ibuprofen in Gabonese children with uncomplicated falciparum malaria: a randomized, double-blind, placebo-controlled trial

PubMed Central

Matsiégui, Pierre-Blaise; Missinou, Michel A; Necek, Magdalena; Mavoungou, Elie; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter G

2008-01-01

Background Antipyretic drugs are widely used in children with fever, though there is a controversy about the benefit of reducing fever in children with malaria. In order to assess the effect of ibuprofen on fever compared to placebo in children with uncomplicated Plasmodium falciparum malaria in Gabon, a randomized double blind placebo controlled trial, was designed. Methods Fifty children between two and seven years of age with uncomplicated malaria were included in the study. For the treatment of fever, all patients "received" mechanical treatment when the temperature rose above 37.5°C. In addition to the mechanical treatment, continuous fanning and cooling blanket, patients were assigned randomly to receive ibuprofen (7 mg/kg body weight, every eight hours) or placebo. Results The fever clearance time using a fever threshold of 37.5°C was similar in children receiving ibuprofen compared to those receiving placebo. The difference was also not statistically significant using a fever threshold of 37.8°C or 38.0°C. However, the fever time and the area under the fever curve were significantly smaller in the ibuprofen group compared to the placebo group. Conclusion Ibuprofen is effective in reducing the time with fever. The effect on fever clearance is less obvious and depends on definition of the fever threshold. Trial registration The trial registration number is: NCT00167713 PMID:18503714

Formulation of Novel Layered Sodium Carboxymethylcellulose Film Wound Dressings with Ibuprofen for Alleviating Wound Pain

PubMed Central

Vinklárková, Lenka; Vetchý, David; Bernatonienė, Jurga

2015-01-01

Effective assessment and management of wound pain can facilitate both improvements in healing rates and overall quality of life. From a pharmacological perspective, topical application of nonsteroidal anti-inflammatory drugs in the form of film wound dressings may be a good choice. Thus, the aim of this work was to develop novel layered film wound dressings containing ibuprofen based on partially substituted fibrous sodium carboxymethylcellulose (nonwoven textile Hcel NaT). To this end, an innovative solvent casting method using a sequential coating technique has been applied. The concentration of ibuprofen which was incorporated as an acetone solution or as a suspension in a sodium carboxymethylcellulose dispersion was 0.5 mg/cm2 and 1.0 mg/cm2 of film. Results showed that developed films had adequate mechanical and swelling properties and an advantageous acidic surface pH for wound application. An in vitro drug release study implied that layered films retained the drug for a longer period of time and thus could minimize the frequency of changing the dressing. Films with suspended ibuprofen demonstrated higher drug content uniformity and superior in vitro drug release characteristics in comparison with ibuprofen incorporation as an acetone solution. Prepared films could be potential wound dressings for the effective treatment of wound pain in low exuding wounds. PMID:26090454

[Cost-effectiveness analysis of celecoxib versus non-selective non-steroidal anti-inflammatory drug therapy for the treatment of osteoarthritis in Spain: A current perspective].

PubMed

De Lossada, A; Oteo-Álvaro, Á; Giménez, S; Oyagüez, I; Rejas, J

2016-01-01

To assess the cost-effectiveness of celecoxib and non-selective non-steroidal anti-inflammatory drugs for the treatment of osteoarthritis in clinical practice in Spain. A decision-tree model using distribution, doses, treatment duration and incidence of GI and CV events observed in the pragmatic PROBE-designed «GI-Reasons» trial was used for cost-effectiveness. Effectiveness was expressed in terms of event averted and quality-adjusted life-years (QALY) gained. QALY were calculated based on utility decrement in case of any adverse events reported in GI-Reasons trial. The National Health System perspective in Spain was applied; cost calculations included current prices of drugs plus cost of adverse events occurred. The analysis was expressed as an incremental cost-effectiveness ratio per QALY gained and per event averted. One-way and probabilistic analyses were performed. Compared with non-selective non-steroidal anti-inflammatory drugs, at current prices, celecoxib treatment had higher overall treatment costs €201 and €157, respectively. However, celecoxib was associated with a slight increase in QALY gain and significantly lower incidence of gastrointestinal events (p<.001), with mean incremental cost-effectiveness ratio of €13,286 per QALY gained and €4,471 per event averted. Sensitivity analyses were robust, and confirmed the results of the base case. Celecoxib at current price may be considered as a cost-effective alternative vs. non-selective non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis in daily practice in the Spanish NHS. Copyright © 2015 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Comparative study of the efficacy and safety of paracetamol, ibuprofen, and indomethacin in closure of patent ductus arteriosus in preterm neonates.

PubMed

El-Mashad, Abd El-Rahman; El-Mahdy, Heba; El Amrousy, Doaa; Elgendy, Marwa

2017-02-01

In this prospective study, we compared the efficacy and side effects of indomethacin, ibuprofen, and paracetamol in patent ductus arteriosus (PDA) closure in preterm neonates. Three hundred preterm neonates with hemodynamically significant PDA (hs-PDA) admitted at our neonatal intensive care unit were enrolled in the study. They were randomized into three groups. Group I (paracetamol group) received 15 mg/kg/6 h IV paracetamol infusion for 3 days. Group II (ibuprofen group) received 10 mg/kg IV ibuprofen infusion followed by 5 mg/kg/day for 2 days. Group III (indomethacin group) received 0.2 mg/kg/12 h indomethacin IV infusion for three doses. Laboratory investigations such as renal function test, liver function test, complete blood count, and blood gases were conducted in addition to echocardiographic examinations. All investigations were done before and 3 days after treatment. There was no significant difference between all groups regarding efficacy of PDA closure (P = 0.868). There was a significant increase in serum creatinine levels and serum blood urea nitrogen (BUN) in the ibuprofen and indomethacin groups (P < 0.001). There was a significant reduction in platelet count and urine output (UOP) in both ibuprofen and indomethacin groups (P < 0.001). There was a significant increase in bilirubin levels in only the ibuprofen group (P = 0.003). No significant difference of hemoglobin (HB) level or liver enzymes in all groups (P > 0.05). Ventilatory settings improved significantly in patients with successful closure of PDA than those with failed PDA closure (P < 0.001). Paracetamol is as effective as indomethacin and ibuprofen in closure of PDA in preterm neonates and has less side effects mainly on renal function, platelet count, and GIT bleeding. What is Known: • Hemodynamically significant patent ductus arteriosus has many complications for preterm and low birth weight neonates and better to be closed. Many drugs were used for medical

Demonstration of synergy with fluconazole and either ibuprofen, sodium salicylate, or propylparaben against Candida albicans in vitro.

PubMed

Scott, E M; Tariq, V N; McCrory, R M

1995-12-01

The combination of fluconazole with either ibuprofen, sodium salicylate, or propylparaben resulted in synergistic activity (fractional inhibitory index, < 0.5) against Candida albicans NCYC 620 in a microdilution checkerboard assay. Synergism between miconazole and ibuprofen was also demonstrated. In three or four clinical isolates of C. albicans from AIDS patients, the combination of fluconazole and ibuprofen was synergistic. Preparation of the inoculum and the growth conditions used were those recommended by the National Committee for Clinical Laboratory Standards for susceptibility testing. A visual estimation of total inhibition of growth and determination of an 80% reduction in the optical density at 492 nm compared with those for the control were taken as endpoints for the calculation of synergy, and a good correlation between both estimates was demonstrated.

Separation of the enantiomers of ibuprofen and its major phase I metabolites in urine using capillary electrophoresis.

PubMed

Bjørnsdottir, I; Kepp, D R; Tjørnelund, J; Hansen, S H

1998-03-01

A capillary electrophoresis method for determination of the enantiomers of ibuprofen and its major phase I metabolites: 2'-hydroxyibuprofen and 2'-carboxyibuprofen in urine samples have been developed. Cyclodextrins and linear dextrins have been investigated as chiral selectors. Simultaneous chiral separation of the enantiomers of ibuprofen, 2'-hydroxyibuprofen and 2'-carboxyibuprofen was obtained using a mixture of dextrin 10 and heptakis (2,3,6-tri-O-methyl)-beta-cyclodextrin in a 2-[N-morpholino]ethanesulphonic acid buffer, pH 5.26. The electroosmotic flow was reversed using hexadimethrine bromide as a buffer additive. The method can be used for the determination of the free enantiomers of ibuprofen, 2'-hydroxyibuprofen and 2'-carboxyibuprofen as well as for the indirect determination of their glucuronic acid conjugates in urine samples.

Treatment with acetaminophen/paracetamol or ibuprofen alleviates post-dose symptoms related to intravenous infusion with zoledronic acid 5 mg.

PubMed

Wark, J D; Bensen, W; Recknor, C; Ryabitseva, O; Chiodo, J; Mesenbrink, P; de Villiers, T J

2012-02-01

Patients treated with intravenous zoledronic acid 5 mg for osteoporosis may experience post-dose influenza-like symptoms. Oral acetaminophen/paracetamol or ibuprofen administered 4 h post-infusion reduced the proportion of patients with increased oral temperature and worsening post-infusion symptom scores vs. placebo, thus providing an effective strategy for the treatment of such symptoms. Once-yearly intravenous zoledronic acid 5 mg is a safe and effective treatment for postmenopausal osteoporosis. This study assessed whether transient influenza-like post-dose symptoms associated with intravenous infusion of zoledronic acid can be reduced by post-dose administration of acetaminophen/paracetamol or ibuprofen. In an international, multicenter, randomized, double-blind, double-dummy parallel-group study, bisphosphonate-naïve postmenopausal women with osteopenia (n = 481) were randomized to receive zoledronic acid 5 mg + acetaminophen/paracetamol (n = 135), ibuprofen (n = 137) or placebo (n = 137), or placebo + placebo (n = 72). Acetaminophen/paracetamol and ibuprofen were administered every 6 h for 3 days beginning 4 h post-infusion. The proportion of patients with increased oral temperature (≥1°C above 37.5°C) and with worsening post-infusion symptom scores over 3 days was significantly lower in patients receiving ibuprofen (36.8% and 48.5%) or acetaminophen/paracetamol (37.3% and 46.3%) vs. those receiving placebo (63.5% and 75.9%, respectively; all p < 0.0001) compared with background rates of 11.1% and 16.7%, respectively, in the absence of any active treatment. Overall incidence of adverse events was comparable for patients receiving acetaminophen/paracetamol or ibuprofen. Oral acetaminophen/paracetamol or ibuprofen effectively managed the transient influenza-like symptoms associated with zoledronic acid 5 mg.

Intravenous ibuprofen: the first injectable product for the treatment of pain and fever

PubMed Central

Bookstaver, P Brandon; Miller, April D; Rudisill, Celeste N; Norris, LeAnn B

2010-01-01

This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in a series of post-operative patient populations. Two recent studies have also noted the improvement in fever curves in critically ill and burn patients. These data, along with pharmacokinetic and pharmacologic properties, are explored in this review, which addresses the clinical utility of a parenteral NSAID in a hospitalized patient for post-operative pain management and fever reduction. Further data on intravenous ibuprofen are needed to define long-term utilization, management of acute pain, and use in special populations. PMID:21197311

Spectrofluorimetric assessment of chlorzoxazone and ibuprofen in pharmaceutical formulations by using Eu-tetracycline HCl optical sensor doped in sol-gel matrix.

PubMed

Attia, M S; Ramsis, M N; Khalil, L H; Hashem, S G

2012-03-01

A novel, simple, sensitive and selective spectrofluorimetric method was developed for the determination of trace amounts of chlorzoxazone and Ibuprofen in pharmaceutical tablets using optical sensor Eu-Tetracycline HCl doped in sol-gel matrix. The chlorzoxazone or Ibuprofen can remarkably enhance the luminescence intensity of Eu-Tetracycline HCl complex doped in a sol-gel matrix in dimethylformamide (DMF) at pH 9.7 and 6.3, respectively, λ(ex) = 400 nm. The enhancing of luminescence intensity peak of Eu-Tetracycline HCl complex at 617 nm is proportional to the concentration of chlorzoxazone or Ibuprofen a result that suggested profitable application as a simple optical sensor for chlorzoxazone or Ibuprofen assessment. The dynamic ranges found for the determination of chlorzoxazone and Ibuprofen concentration are 5 × 10(-9)-1 × 10(-4) and 1 × 10(-8)-7 × 10(-5) mol L(-1), and the limit of detection (LOD) and quantitation limit of detection (LOQ) are 3.1 × 10(-10), 9.6 × 10(-10) and 5.6 × 10(-10), 1.7 × 10(-9) mol L(-1), respectively.

Efficacy of nano- and microemulsion-based topical gels in delivery of ibuprofen: an in vivo study.

PubMed

Azizi, Mosayeb; Esmaeili, Fariba; Partoazar, Alireza; Ejtemaei Mehr, Shahram; Amani, Amir

2017-03-01

Nanoemulsion has shown many advantages in drug delivery systems. In this study, for the first time, analgesic and anti-inflammatory properties of a nanomelusion of almond oil with and without ibuprofen was compared with corresponding microemulsion and commercial topical gel of the drug using formalin and carrageenan tests, respectively. Almond oil (oil phase) was mixed with Tween 80 and Span 80 (surfactants), and ethanol (co-surfactant) and them distilled water (aqueous phase) was then added to the mixture at once. Prepared nanoemulsions were pre-emulsified into a 100 ml beaker using magnet/stirrer (1000 rpm). Then, using a probe ultrasonicator (Hielscher UP400s, Hielscher, Ringwood, NJ) the nanoemulsions were formed. The optimised nanoemulsion formulation containing 2.5% ibuprofen, showed improved analgesic and anti-inflammatory effects compared with commercial product and corresponding microemulsion product containing 5% ibuprofen (i.e. twice the content of ibuprofen in the nanoemulsion) in vivo. The nanoemulsion preparation showed superior analgesic activities during chronic phase. Also, it decreased the inflammation from the first hour, while the microemulsion and the commercial product started to show their anti-inflammatory effects after 2 and 3 h, respectively. Our finding suggests that the size of the emulsion particles must be considered as an important factor in topical drug delivery systems.

[Has the use of antipyretics been modified after the introduction of different concentrations of ibuprofen into the market?].

PubMed

García Blanes, C P; Rodríguez-Cantón Pascual, P; Morales-Carpi, C; Morales-Olivas, F J

2014-12-01

Due to the emergence of new pharmaceutical presentations of ibuprofen (40 mg/ml), an analysis was made on the use of antipyretics in pediatric outpatient in Spain. A cross-sectional, observational, descriptive study was carried out on a sample of children under 14 years old with treated febrile syndrome, seen in the Emergency Room of the Hospital General Universitario de Valencia from November 2012 to January 2013. Of the 217 children included, 144 were treated with paracetamol or ibuprofen, 69 received both drugs, and one received paracetamol and metamizol. There were 58.7% of exposures to paracetamol and 40.9% to ibuprofen. The parents decided the use of antipyretics in 63.2% of cases. In 98 exposures the dose was different from that authorized in the labeling of the drug (off-label use). Ibuprofen was used off-label in 40.2% of cases, mostly by underdosing (35.9%). Paracetamol was used off-label in 29.8% of cases, predominantly overdose (26.8%), with the difference being statistically significant. No significant differences were observed in the off-label use in either monotherapy or combined use. There were also no differences when antipyretics prescribed by doctors or given directly by parents were evaluated separately. The majority of children with treated febrile syndrome seen in the Emergency Room were receiving antipyretic drugs after a parental decision. Paracetamol is the most commonly used drug and one in three children received it simultaneously with ibuprofen. The antipyretics were used off label in one-third of the cases. Off label use of ibuprofen is increasing, and is probably due to the existence of different pharmaceutical presentations. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Early and late effects of Ibuprofen on mouse sperm parameters, chromatin condensation, and DNA integrity in mice.

PubMed

Roodbari, Fatemeh; Abedi, Nahid; Talebi, Ali Reza

2015-11-01

There are few studies indicating the detrimental effects of ibuprofen on sperm fertility potential and DNA integrity. To determine the effects of Ibuprofen on sperm parameters, chromatin condensation and DNA integrity of mice. In this experimental study, 36 adult male mice with average weight 37 gr were divided into three groups, including control (group I, n=12), normal dosage of ibuprofen (group II, n=12) and high dosage (group III, n=12). Ibuprofen with different doses was dissolved in daily water of animals. After 35, 70 and 105 days, the cauda epididymis of mice were cut and incubated in Ham's F10 media. Sperm samples were analyzed for parameters (motility, morphology and count), DNA integrity (SCD test) and chromatin condensation (chromomycin A3 and Aniline blue staining). After 35 days, in addition to above mentioned sperm parameters, all of the treated mice showed statistically significant increase in spermatozoa with immature chromatin (P<0.05). However, after 70 days, the rate of sperm DNA fragmentation assessed by SCD was increased in group II (66.5±0.7) and the percentage of immature spermatozoa (AB(+) and CMA3(+)) was higher in group III (77.5±0.7 and 49.5±6.3 respectively) than other groups. After 105 days, the AB(+) spermatozoa were increased in both normal dose and high dose groups. Ibuprofen may cause a significant reduction in sperm parameters and sperm chromatin/DNA integrity in mice. It should be noted that these deleterious effects are dose-dependent and can be seen in early and late stage of drug treatments.

Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells.

PubMed

Villa, Valentina; Thellung, Stefano; Corsaro, Alessandro; Novelli, Federica; Tasso, Bruno; Colucci-D'Amato, Luca; Gatta, Elena; Tonelli, Michele; Florio, Tullio

2016-01-01

Activation of microglia is a central event in the atypical inflammatory response occurring during prion encephalopathies. We report that the prion protein fragment encompassing amino acids 90-231 (PrP90-231), a model of the neurotoxic activity of the pathogenic prion protein (PrP(Sc)), causes activation of both primary microglia cultures and N9 microglial cells in vitro. This effect was characterized by cell proliferation arrest and induction of a secretory phenotype, releasing prostaglandin E2 (PGE2) and nitric oxide (NO). Conditioned medium from PrP90-231-treated microglia induced in vitro cytotoxicity of A1 mesencephalic neurons, supporting the notion that soluble mediators released by activated microglia contributes to the neurodegeneration during prion diseases. The neuroinflammatory role of COX activity, and its potential targeting for anti-prion therapies, was tested measuring the effects of ketoprofen and celecoxib (preferential inhibitors of COX1 and COX2, respectively) on PrP90-231-induced microglial activation. Celecoxib, but not ketoprofen significantly reverted the growth arrest as well as NO and PGE2 secretion induced by PrP90-231, indicating that PrP90-231 pro-inflammatory response in microglia is mainly dependent on COX2 activation. Taken together, these data outline the importance of microglia in the neurotoxicity occurring during prion diseases and highlight the potentiality of COX2-selective inhibitors to revert microglia as adjunctive pharmacological approach to contrast the neuroinflammation-dependent neurotoxicity.

Single dose oral analgesics for acute postoperative pain in adults

PubMed Central

Moore, R Andrew; Derry, Sheena; McQuay, Henry J; Wiffen, Philip J

2014-01-01

mg, diflunisal 125 mg, etoricoxib 60 mg, fenbufen, and indometacin. Where there was adequate information for drug/dose combinations (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable. Reliable results were obtained for 46 drug/dose combinations in all painful postsurgical conditions; 45 in dental pain and 14 in other painful conditions. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours in the same pain condition. Participants reporting at least one adverse event were few and generally no different between active drug and placebo, with a few exceptions, principally for aspirin and opioids. Drug/dose combinations with good (low) NNTs were ibuprofen 400 mg (2.5; 95% confidence interval (CI) 2.4 to 2.6), diclofenac 50 mg (2.7; 95% CI 2.4 to 3.0), etoricoxib 120 mg (1.9; 95% CI 1.7 to 2.1), codeine 60 mg + paracetamol 1000 mg (2.2; 95% CI 1.8 to 2.9), celecoxib 400 mg (2.5; 95% CI 2.2 to 2.9), and naproxen 500/550 mg (2.7; 95% CI 2.3 to 3.3). Long duration of action (8 hours) was found for etoricoxib 120 mg, diflunisal 500 mg, oxycodone 10 mg + paracetamol 650 mg, naproxen 500/550 mg, and celecoxib 400 mg. Not all participants had good pain relief and for many drug/dose combinations 50% or more did not achieve at last 50% maximum pain relief over four to six hours. Authors’ conclusions There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias

Intravenous Ibuprofen for Treatment of Post-Operative Pain: A Multicenter, Double Blind, Placebo-Controlled, Randomized Clinical Trial

PubMed Central

Escontrela Rodriguez, Blanca; Planas Roca, Antonio; Martínez Ruiz, Alberto

2016-01-01

Background Non-steroidal anti-inflammatory drugs are often used as components of multimodal therapy for postoperative pain management, but their use is currently limited by its side effects. The specific objective of this study was to evaluate the efficacy and safety of a new formulation of intravenous (IV) ibuprofen for the management of postoperative pain in a European population. Methods and Findings A total of 206 patients from both abdominal and orthopedic surgery, were randomly assigned in 1:1 ratio to receive 800 mg IV-ibuprofen or placebo every 6 hours; all patients had morphine access through a patient controlled analgesia pump. The primary outcome measure was median morphine consumption within the first 24 hours following surgery. The mean±SEM of morphine requirements was reduced from 29,8±5,25 mg to 14,22±3,23 mg (p = 0,015) and resulted in a decrease in pain at rest (p = 0,02) measured by Visual Analog Scale (VAS) from mean±SEM 3.34±0,35 to 0.86±0.24, and also in pain during movement (p = 0,02) from 4.32±0,36 to 1.90±0,30 in the ibuprofen treatment arm; while in the placebo group VAS score at rest ranged from 4.68±0,40 to 2.12±0,42 and during movement from 5.66±0,42 to 3.38±0,44. Similar treatment-emergent adverse events occurred across both study groups and there was no difference in the overall incidence of these events. Conclusions Perioperative administration of IV-Ibuprofen 800 mg every 6 hours in abdominal surgery patient’s decreases morphine requirements and pain score. Furthermore IV-Ibuprofen was safe and well tolerate. Consequently we consider appropriate that protocols for management of postoperative pain include IV-Ibuprofen 800 mg every 6 hours as an option to offer patients an analgesic benefit while reducing the potentially risks associated with morphine consumption. Trial Registration EU Clinical Trials Register 2011-005007-33 PMID:27152748

Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth.

PubMed

Bailey, Edmund; Worthington, Helen V; van Wijk, Arjen; Yates, Julian M; Coulthard, Paul; Afzal, Zahid

2013-12-12

Both paracetamol and ibuprofen are commonly used analgesics for the relief of pain following the surgical removal of lower wisdom teeth (third molars). In 2010, a novel analgesic (marketed as Nuromol) containing both paracetamol and ibuprofen in the same tablet was launched in the United Kingdom, this drug has shown promising results to date and we have chosen to also compare the combined drug with the single drugs using this model. In this review we investigated the optimal doses of both paracetamol and ibuprofen via comparison of both and via comparison with the novel combined drug. We have taken into account the side effect profile of the study drugs. This review will help oral surgeons to decide on which analgesic to prescribe following wisdom tooth removal. To compare the beneficial and harmful effects of paracetamol, ibuprofen and the novel combination of both in a single tablet for pain relief following the surgical removal of lower wisdom teeth, at different doses and administered postoperatively. We searched the Cochrane Oral Health Group'sTrials Register (to 20 May 2013); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 4); MEDLINE via OVID (1946 to 20 May 2013); EMBASE via OVID (1980 to 20 May 2013) and the metaRegister of Controlled Trials (to 20 May 2013). We checked the bibliographies of relevant clinical trials and review articles for further studies. We wrote to authors of the identified randomised controlled trials (RCTs), and searched personal references in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied to the searches of the electronic databases. Only randomised controlled double-blinded clinical trials were included. Cross-over studies were included provided there was a wash out period of at least 14 days. There had to be a direct comparison in the trial of two or more of the trial drugs at any dosage. All trials used the third molar pain model. All trials

Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

NASA Technical Reports Server (NTRS)

Cheung, E. V.; Tidball, J. G.

2003-01-01

OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

A multicentre, randomized, placebo- and active-controlled trial comparing the efficacy and safety of topical ketoprofen in Transfersome gel (IDEA-033) with ketoprofen-free vehicle (TDT 064) and oral celecoxib for knee pain associated with osteoarthritis.

PubMed

Conaghan, Philip G; Dickson, John; Bolten, Wolfgang; Cevc, Gregor; Rother, Matthias

2013-07-01

To assess the efficacy and safety of 12-week treatment with ketoprofen in ultradeformable phospholipid vesicles in patients with OA knee pain and to compare the efficacy with that of ketoprofen-free vehicle and celecoxib. METHODS; A multicentre, double-blind controlled study in which patients with knee OA and moderate pain were randomized to one of the six arms: topical ketoprofen 50 or 100 mg in ultradeformable vesicles (IDEA-033), 2.2 or 4.4 g ketoprofen-free vehicle (TDT 064), oral celecoxib 100 mg or matching oral placebo, all bd. The primary outcome was change from baseline in the WOMAC pain subscale at week 12. A total of 1395 patients received treatment. Baseline mean WOMAC pain scores ranged from 4.7 to 4.8 across groups. The mean reduction in WOMAC pain score at week 12 was -1.9 (-40.8%) for ketoprofen 50 mg, -1.9 (-40.9%) for ketoprofen 100 mg, -1.9 (-39.8%) for 2.2 g TDT 064, -1.8 (-37.8%) for 4.4 g TDT 064, -1.9 (-40.4%) for celecoxib and -1.4 (-29.3%) for oral placebo. IDEA-033 was not statistically superior to TDT 064. All topical treatments were statistically superior to oral placebo and non-inferior to celecoxib. The most frequent types of treatment-related adverse events reported were gastrointestinal for oral (15.9% for celecoxib) and dermal for topical applications (12.2% for ketoprofen 100 mg). IDEA-033 was not superior to ketoprofen-free vehicle, but both formulations were superior to oral placebo and non-inferior to celecoxib in reducing OA knee pain. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00716547.

Demonstration of synergy with fluconazole and either ibuprofen, sodium salicylate, or propylparaben against Candida albicans in vitro.

PubMed Central

Scott, E M; Tariq, V N; McCrory, R M

1995-01-01

The combination of fluconazole with either ibuprofen, sodium salicylate, or propylparaben resulted in synergistic activity (fractional inhibitory index, < 0.5) against Candida albicans NCYC 620 in a microdilution checkerboard assay. Synergism between miconazole and ibuprofen was also demonstrated. In three or four clinical isolates of C. albicans from AIDS patients, the combination of fluconazole and ibuprofen was synergistic. Preparation of the inoculum and the growth conditions used were those recommended by the National Committee for Clinical Laboratory Standards for susceptibility testing. A visual estimation of total inhibition of growth and determination of an 80% reduction in the optical density at 492 nm compared with those for the control were taken as endpoints for the calculation of synergy, and a good correlation between both estimates was demonstrated. PMID:8592988

Application of the ratio difference spectrophotometry to the determination of ibuprofen and famotidine in their combined dosage form: comparison with previously published spectrophotometric methods.

PubMed

Zaazaa, Hala E; Elzanfaly, Eman S; Soudi, Aya T; Salem, Maissa Y

2015-05-15

Ratio difference spectrophotometric method was developed for the determination of ibuprofen and famotidine in their mixture form. Ibuprofen and famotidine were determined in the presence of each other by the ratio difference spectrophotometric (RD) method where linearity was obtained from 50 to 600μg/mL and 2.5 to 25μg/mL for ibuprofen and famotidine, respectively. The suggested method was validated according to ICH guidelines and successfully applied for the analysis of ibuprofen and famotidine in their pharmaceutical dosage forms without interference from any additives or excipients. Copyright © 2015 Elsevier B.V. All rights reserved.

Efficacy and safety of oral paracetamol versus oral ibuprofen for closure of patent ductus arteriosus in preterm infants: a randomized controlled trial.

PubMed

El-Farrash, Rania A; El Shimy, Mohammed S; El-Sakka, Abeer S; Ahmed, Manal G; Abdel-Moez, Dina G

2018-05-09

The objective of this study is to evaluate the efficacy and safety of oral paracetamol versus oral ibuprofen in the treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. An interventional randomized case-control study, registered in ClinicalTrials.gov (NCT03265782), was conducted on 60 preterm infants with gestational age ≤34 weeks, postnatal age of 2-7 d and color Doppler echocardiographic evidence of hsPDA. Neonates were randomly assigned to two groups: 30 received oral ibuprofen and 30 received oral paracetamol. With failure of ductal closure, a second course of ibuprofen or paracetamol was given. The included newborns were subjected to detailed history, clinical examination, laboratory investigations that included complete blood count, renal, and liver function tests and echocardiographic evaluation. Oral paracetamol was as effective as ibuprofen for the closure of patent ductus arteriosus (PDA) with one course of treatment (p > .05). Moreover, oral paracetamol was superior to ibuprofen among neonates who needed second course of treatment with significant decrease in end diastolic flow velocity in the left pulmonary artery (0.35 ± 0.09 versus 0.19 ± 0.06, p = .014), right ventricular systolic pressure (40.50 ± 12.91 versus 20.50 ± 0.58, p = .016) and left atrium to aortic root ratio (1.23 ± 0.14 versus 1.07 ± 0.04, p = .046) when compared to ibuprofen group. Furthermore, the mean difference between pre- and post-treatment PDA size was significantly higher in the paracetamol group compared with ibuprofen group after the second course of treatment (1.07 ± 0.32 versus 0.73 ± 0.38, p = .024). Oral paracetamol was comparable with ibuprofen in terms of the rate of non-surgical ductal closure [28 (93.3%) versus 24 (80%), p = .591]. In addition, oral paracetamol was as safe as oral ibuprofen in terms of gastrointestinal perforation or bleeding, necrotizing

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot.

PubMed

Kitson, Philip J; Glatzel, Stefan; Cronin, Leroy

2016-01-01

An automated synthesis robot was constructed by modifying an open source 3D printing platform. The resulting automated system was used to 3D print reaction vessels (reactionware) of differing internal volumes using polypropylene feedstock via a fused deposition modeling 3D printing approach and subsequently make use of these fabricated vessels to synthesize the nonsteroidal anti-inflammatory drug ibuprofen via a consecutive one-pot three-step approach. The synthesis of ibuprofen could be achieved on different scales simply by adjusting the parameters in the robot control software. The software for controlling the synthesis robot was written in the python programming language and hard-coded for the synthesis of ibuprofen by the method described, opening possibilities for the sharing of validated synthetic 'programs' which can run on similar low cost, user-constructed robotic platforms towards an 'open-source' regime in the area of chemical synthesis.

The digital code driven autonomous synthesis of ibuprofen automated in a 3D-printer-based robot

PubMed Central

Kitson, Philip J; Glatzel, Stefan

2016-01-01

An automated synthesis robot was constructed by modifying an open source 3D printing platform. The resulting automated system was used to 3D print reaction vessels (reactionware) of differing internal volumes using polypropylene feedstock via a fused deposition modeling 3D printing approach and subsequently make use of these fabricated vessels to synthesize the nonsteroidal anti-inflammatory drug ibuprofen via a consecutive one-pot three-step approach. The synthesis of ibuprofen could be achieved on different scales simply by adjusting the parameters in the robot control software. The software for controlling the synthesis robot was written in the python programming language and hard-coded for the synthesis of ibuprofen by the method described, opening possibilities for the sharing of validated synthetic ‘programs’ which can run on similar low cost, user-constructed robotic platforms towards an ‘open-source’ regime in the area of chemical synthesis. PMID:28144350

Efficacy and safety of epicutaneous ketoprofen in Transfersome (IDEA‐033) versus oral celecoxib and placebo in osteoarthritis of the knee: multicentre randomised controlled trial

PubMed Central

Rother, Matthias; Lavins, Bernard J; Kneer, Werner; Lehnhardt, Klaus; Seidel, Egbert J; Mazgareanu, Stefan

2007-01-01

Objective To compare epicutaneous ketoprofen in Transfersome (ultra‐deformable vesicles, IDEA‐033) versus oral celecoxib and placebo for relief of signs and symptoms in knee osteoarthritis. Methods This was a multicentre, randomised, double‐blind, controlled trial; 397 patients with knee osteoarthritis participated and 324 completed the trial. They were randomly assigned 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (n = 138), 100 mg oral celecoxib plus placebo gel (n = 132), or both placebo formulations (n = 127) twice daily for 6 weeks. Primary efficacy outcome measures were the changes from baseline to end of the study on the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain subscale, physical function subscale and patient global assessment (PGA) of response. Results The mean WOMAC pain subscale scores in the intent to treat population were reduced by 18.2 (95% confidence interval −22.1 to −14.3), 20.3 (−24.3 to −16.2) and 9.9 (−13.9 to −5.8) in the IDEA‐033, celecoxib and placebo groups, respectively, and the physical function subscale score by 14.6 (−18.1 to −11.0), 16.6 (−20.2 to −13.0) and 10.2 (−13.8 to −6.6), respectively. The mean PGA of response scores were 1.8 (1.6 to 2.1), 1.7 (1.5 to 1.9) and 1.3 (1.1 to 1.5), respectively. The differences in change between IDEA‐033 and placebo were statistically significant for pain subscale (p<0.01) and PGA of response (p<0.01). Gastrointestinal adverse events for IDEA‐033 were similar to placebo. Conclusion IDEA‐033 is superior to placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. PMID:17363401

Simultaneous Determination of Celecoxib, Erlotinib, and its Metabolite Desmethyl-Erlotinib (OSI-420) in Rat Plasma by Liquid chromatography/Tandem Mass Spectrometry with Positive/Negative Ion-Switching Electrospray Ionisation

PubMed Central

Thappali, Satheeshmanikandan R. S.; Varanasi, Kanthikiran; Veeraraghavan, Sridhar; Arla, Rambabu; Chennupati, Sandhya; Rajamanickam, Madheswaran; Vakkalanka, Swaroop; Khagga, Mukkanti

2012-01-01

A new method for the simultaneous determination of celecoxib, erlotinib, and its active metabolite desmethyl-erlotinib (OSI-420) in rat plasma, by liquid chromatography/tandem mass spectrometry with positive/negative ion-switching electrospray ionization mode, was developed and validated. Protein precipitation with methanol was selected as the method for preparing the samples. The analytes were separated on a reverse-phase C18 column (50mm×4.6mm i.d., 3μ) using methanol: 2 mM ammonium acetate buffer, and pH 4.0 as the mobile phase at a flow rate 0.8 mL/min. Sitagliptin and Efervirenz were used as the internal standards for quantification. The determination was carried out on a Theremo Finnigan Quantam ultra triple-quadrupole mass spectrometer, operated in selected reaction monitoring (SRM) mode using the following transitions monitored simultaneously: positive m/z 394.5→278.1 for erlotinib, m/z 380.3→278.1 for desmethyl erlotinib (OSI-420), and negative m/z −380.1→ −316.3 for celecoxib. The limits of quantification (LOQs) were 1.5 ng/mL for Celecoxib, erlotinib, and OSI-420. Within- and between-day accuracy and precision of the validated method were within the acceptable limits of < 15% at all concentrations. The quantitation method was successfully applied for the simultaneous estimation of celecoxib, erlotinib, and desmethyl erlotinib in a pharmacokinetic study in Wistar rats. PMID:23008811

Timing of Ibuprofen Use and Bone Mineral Density Adaptations to Exercise Training

PubMed Central

Kohrt, Wendy M; Barry, Daniel W; Van Pelt, Rachael E; Jankowski, Catherine M; Wolfe, Pamela; Schwartz, Robert S

2010-01-01

Prostaglandins (PGs) are essential signaling factors in bone mechanotransduction. In animals, inhibition of the enzyme responsible for PG synthesis (cyclooxygenase) by nonsteroidal anti-inflammatory drugs (NSAIDs) blocks the bone-formation response to loading when administered before, but not immediately after, loading. The aim of this proof-of-concept study was to determine whether the timing of NSAID use influences bone mineral density (BMD) adaptations to exercise in humans. Healthy premenopausal women (n = 73) aged 21 to 40 years completed a supervised 9-month weight-bearing exercise training program. They were randomized to take (1) ibuprofen (400 mg) before exercise, placebo after (IBUP/PLAC), (2) placebo before, ibuprofen after (PLAC/IBUP), or (3) placebo before and after (PLAC/PLAC) exercise. Relative changes in hip and lumbar spine BMD from before to after exercise training were assessed using a Hologic Delphi-W dual-energy X-ray absorptiometry (DXA) instrument. Because this was the first study to evaluate whether ibuprofen use affects skeletal adaptations to exercise, only women who were compliant with exercise were included in the primary analyses (IBUP/PLAC, n = 17; PLAC/PLAC, n = 23; and PLAC/IBUP, n = 14). There was a significant effect of drug treatment, adjusted for baseline BMD, on the BMD response to exercise for regions of the hip (total, p < .001; neck, p = .026; trochanter, p = .040; shaft, p = .019) but not the spine (p = .242). The largest increases in BMD occurred in the group that took ibuprofen after exercise. Total-hip BMD changes averaged –0.2% ± 1.3%, 0.4% ± 1.8%, and 2.1% ± 1.7% in the IBUP/PLAC, PLAC/PLAC, and PLAC/IBUP groups, respectively. This preliminary study suggests that taking NSAIDs after exercise enhances the adaptive response of BMD to exercise, whereas taking NSAIDs before may impair the adaptive response. © 2010 American Society for Bone and Mineral Research. PMID:20200939

Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells

PubMed Central

Lampiasi, Nadia; Cusimano, Antonella; Azzolina, Antonina; McCubrey, James A.; Montalto, Giuseppe

2013-01-01

Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of the combination, we investigated the expression profile of the combination-treated liver cancer cell lines using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell-cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell lines displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semi-quantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomic analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies. PMID:23776502

Comparison of two dose regimens of ibuprofen for the closure of patent ductus arteriosus in preterm newborns.

PubMed

Dornelles, Laura Vargas; Corso, Andréa Lúcia; Silveira, Rita de Cássia; Procianoy, Renato Soibelmann

2016-01-01

To compare the efficacy of intravenous ibuprofen at high (20-10-10mg/kg/dose) and low doses (10-5-5mg/kg/dose) the closure of patent ductus arteriosus in preterm newborns. A cohort study with historical control of newborns that received high- and low-dose intravenous ibuprofen, from 2010 to 2013 in a neonatal intensive care unit, for closure of the patent ductus arteriosus, documented by echocardiography. Secondary outcomes included the number of ibuprofen cycles, incidence of bronchopulmonary dysplasia, necrotizing enterocolitis, changes in renal function, and death. Seventy-seven patients received three doses of ibuprofen for the treatment of patent ductus arteriosus, with 33 receiving high-dose and 44 low-dose therapy. The ductus closed after the first cycle in 25 (56.8%) low-dose patients and in 17 (51.5%) high-dose patients (p>0.99). Sixteen patients received a second cycle of ibuprofen, and the ductus closed in 50% after low-dose and in 60% after high-dose therapy (p>0.99). Seven patients required surgery for ductus closure, 13.6% in the low-dose group and 3% in the high-dose group (p=0.22). Thirty-nine patients developed bronchopulmonary dysplasia, 50% in the low-dose group and 51.5% in the high-dose group (p>0.99). Twenty-two (50%) low-dose patients died vs. 15 (45.5%) high-dose patients (p=0.86). There was no difference in closure of the ductus arteriosus or occurrence of adverse effects between the two dose regimens. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Distinct enantiomeric signals of ibuprofen and naproxen in treated wastewater and sewer overflow.

PubMed

Khan, Stuart J; Wang, Lili; Hashim, Nor H; McDonald, James A

2014-11-01

Ibuprofen and naproxen are commonly used members of a class of pharmaceuticals known as 2-arylpropionic acids (2-APAs). Both are chiral chemicals and can exist as either of two (R)- and (S)-enantiomers. Enantioselective analyses of effluents from municipal wastewater treatment plants (WWTPs) and from untreated sewage overflow reveal distinctly different enantiomeric fractions for both pharmaceuticals. The (S)-enantiomers of both were dominant in untreated sewage overflow, but the relative proportions of the (R)-enantiomers were shown to be increased in WWTP effluents. (R)-naproxen was below method detection limits (<1 ng.L(-1)) in sewage overflow, but measurable at higher concentrations in WWTP effluents. Accordingly, enantiomeric fractions (EF) for naproxen were consistently 1.0 in sewage overflow, but ranged from 0.7–0.9 in WWTP effluents. Ibuprofen EF ranged from 0.6–0.8 in sewage overflow and receiving waters, and was 0.5 in two WWTP effluents. Strong evidence is provided to indicate that chiral inversion of (S)-2-APAs to produce (R)-2-APAs may occur during wastewater treatment processes. It is concluded that this characterization of the enantiomeric fractions for ibuprofen and naproxen in particular effluents could facilitate the distinction of treated and untreated sources of pharmaceutical contamination in surface waters.

Ibuprofen versus placebo effect on acute kidney injury in ultramarathons: a randomised controlled trial.

PubMed

Lipman, Grant S; Shea, Kate; Christensen, Mark; Phillips, Caleb; Burns, Patrick; Higbee, Rebecca; Koskenoja, Viktoria; Eifling, Kurt; Krabak, Brian J

2017-10-01

Despite concerns that non-steroidal anti-inflammatory drugs (NSAIDs) contribute to acute kidney injury (AKI), up to 75% of ultramarathon runners ingest these during competition. The effect of NSAID on AKI incidence in ultramarathon runners is unclear. Multisite randomised double-blind placebo-controlled trial in the Gobi, Atacama, Ecuador and Sri Lankan deserts to determine whether ibuprofen (400 mg every 4 hours) would be non-inferior to placebo during a 50-mile (80 km) foot race. The primary outcome was incidence of AKI defined as severity categories of 'risk' of injury of 1.5× baseline creatinine (Cr) or 'injury' as 2× Cr, combined to calculate total incidence at the finish line. Non-inferiority margin for difference in AKI rates was defined as 15%. Eighty-nine participants (47% ibuprofen and 53% placebo) were enrolled with similar demographics between groups. The overall incidence of AKI was 44%. Intent-to-treat analysis found 22 (52%) ibuprofen versus 16 (34%) placebo users developed AKI (18% difference, 95% CI -4% to 41%; OR 2.1, 95% CI 0.9 to 5.1) with a number needed to harm of 5.5. Greater severity of AKI was seen with ibuprofen compared with placebo (risk=38% vs 26%; 95% CI -9% to 34%; injury=14% vs 9%; 95% CI -10% to 21%). Slower finishers were less likely to encounter AKI (OR 0.67, 95% CI 0.47 to 0.98) and greater weight loss (-1.3%) increased AKI (OR 1.24, 95% CI 1.00 to 1.63). There were increased rates of AKI in those who took ibuprofen, and although not statistically inferior to placebo by a small margin, there was a number needed to harm of 5.5 people to cause 1 case of AKI. Consideration should therefore be taken before ingesting NSAID during endurance running as it could exacerbate renal injury. NCT02272725. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Organic micropollutants paracetamol and ibuprofen-toxicity, biodegradation, and genetic background of their utilization by bacteria.

PubMed

Żur, Joanna; Piński, Artur; Marchlewicz, Ariel; Hupert-Kocurek, Katarzyna; Wojcieszyńska, Danuta; Guzik, Urszula

2018-06-19

Currently, analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs) are classified as one of the most emerging group of xenobiotics and have been detected in various natural matrices. Among them, monocyclic paracetamol and ibuprofen, widely used to treat mild and moderate pain are the most popular. Since long-term adverse effects of these xenobiotics and their biological and pharmacokinetic activity especially at environmentally relevant concentrations are better understood, degradation of such contaminants has become a major concern. Moreover, to date, conventional wastewater treatment plants (WWTPs) are not fully adapted to remove that kind of micropollutants. Bioremediation processes, which utilize bacterial strains with increased degradation abilities, seem to be a promising alternative to the chemical methods used so far. Nevertheless, despite the wide prevalence of paracetamol and ibuprofen in the environment, toxicity and mechanism of their microbial degradation as well as genetic background of these processes remain not fully characterized. In this review, we described the current state of knowledge about toxicity and biodegradation mechanisms of paracetamol and ibuprofen and provided bioinformatics analysis concerning the genetic bases of these xenobiotics decomposition.

Occurrence and fate of carbamazepine, clofibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen in surface waters.

PubMed

Tixier, Céline; Singer, Heinz P; Oellers, Sjef; Müller, Stephan R

2003-03-15

Although various single-concentration measurements of pharmaceuticals are available in the literature, detailed information on the variation over time of the concentration and the load in wastewater effluents and rivers and on the fate of these compounds in the aquatic environment are lacking. We measured the concentrations of six pharmaceuticals, carbamazepine, clofibric acid, diclofenac, ibuprofen, ketoprofen, and naproxen, in the effluents of three wastewater treatment plants (WWTPs), in two rivers and in the water column of Lake Greifensee (Switzerland) over a time period of three months. In WWTP effluents, the concentrations reached 0.95 microg/L for carbamazepine, 0.06 microg/L for clofibric acid, 0.99 microg/L for diclofenac, 1.3 microg/L for ibuprofen, 0.18 microg/L for ketoprofen, and 2.6 microg/L for naproxen. The relative importance in terms of loads was carbamazepine, followed by diclofenac, naproxen, ibuprofen, clofibric acid, and ketoprofen. An overall removal rate of all these pharmaceuticals was estimated in surface waters, under real-world conditions (in a lake), using field measurements and modeling. Carbamazepine and clofibric acid were fairly persistent. Phototransformation was identified as the main elimination process of diclofenac in the lake water during the study period. With a relatively high sorption coefficient to particles, ibuprofen might be eliminated by sedimentation. For ketoprofen and naproxen, biodegradation and phototransformation might be elimination processes. For the first time, quantitative data regarding removal rates were determined in surface waters under real-world conditions. All these findings are important data for a risk assessment of these compounds in surface waters.

Anaphylaxis to ibuprofen in a 12-year-old boy

PubMed Central

Kay, Emily; Ben-Shoshan, Moshe

2013-01-01

Non-steroidal anti-inflammatory (NSAIDs) drugs are a group of medications acting through cyclooxygenase  (COX-1) and cyclooxygenase  (COX-2) enzymes inhibition. Hypersensitivity reactions to NSAIDs, although not rare, are poorly characterised and often go undiagnosed especially in children. We present in this paper a case of ibuprofen anaphylaxis that exemplifies the challenges involved in diagnosis and management of hypersensitivity reactions to NSAIDs. PMID:23322307

Comparison of the Mortality and In-Hospital Outcomes of Preterm Infants Treated with Ibuprofen for Patent Ductus Arteriosus with or without Clinical Symptoms Attributable to the Patent Ductus Arteriosus at the Time of Ibuprofen Treatment

PubMed Central

2017-01-01

The aim of this study was to assess the differences in the mortality and in-hospital outcomes of preterm infants with < 28 weeks of gestation who received ibuprofen treatment according to the presence of clinical symptoms (any of oliguria, hypotension, or moderate to severe respiratory difficulty) attributable to hemodynamically-significant patent ductus arteriosus (hsPDA) at the time of first ibuprofen treatment. In total, 91 infants born from April 2010 to March 2015 were included. Fourteen infants (15.4%) received ibuprofen treatment when there were clinical symptoms due to hsPDA (clinical symptoms group). In clinical symptoms group, infants were younger (25 [23–27] vs. 26 [23–27] weeks; P = 0.012) and lighter (655 [500–930] vs. 880 [370–1,780] grams; P < 0.001). Also, the clinical risk index for babies (CRIB)-II scores were higher and more infants received invasive ventilator care ≤ 2 postnatal days. More infants received multiple courses of ibuprofen in clinical symptoms group. Although the frequency of secondary patent ductus arteriosus (PDA) ligation and the incidence of bronchopulmonary dysplasia (BPD) was higher in the clinical symptoms group in the univariate analysis, after multivariate logistic regression analysis adjusting for the CRIB-II score, birthweight, birth year, and the invasive ventilator care ≤ 2 postnatal days, there were no significant differences in mortality, frequency of secondary ligation and in-hospital outcomes including necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), BPD or death. Our data suggest that we can hold off on PDA treatment until the clinical symptoms become prominent. PMID:27914140

Silicon containing ibuprofen derivatives with antioxidant and anti-inflammatory activities: An in vivo and in silico study.

PubMed

Pérez, David J; Díaz-Reval, M Irene; Obledo-Benicio, Fernando; Zakai, Uzma I; Gómez-Sandoval, Zeferino; Razo-Hernández, Rodrigo Said; West, Robert; Sumaya-Martínez, María Teresa; Pineda-Urbina, Kayim; Ramos-Organillo, Ángel

2017-11-05

There are many chronic diseases related with inflammation. The chronic inflammation can produce other problems as cancer. Therefore, it is necessary to design drugs with better anti-inflammatory activity than those in the clinic. Likewise, these could be used in chronic treatments with minimum adverse effects. The amide or ester functionality in combination with the insertion of a silyl alkyl moiety is able to improve some drug properties. In this context, the evaluation of a group of silicon containing ibuprofen derivatives (SCIDs) as antioxidants and anti-inflammatory agents is reported. Antioxidant activity was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH⨪), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS • + ) and the Fe(II) chelating ability methods. The anti-inflammatory activity was determined by using the carrageenan induced rat paw edema. The gastrotoxic profile of the SCIDs that displayed significant anti-inflammatory activity was determined by the indomethacin induced ulceration method. The SCIDs performed better than ibuprofen as chelating agents for Fe(II) and as scavengers for the free radicals DPPH• and ABTS • + . On the anti-inflammatory test, compound 4a inhibited the edema up to 87%, while 4d &10b achieved significant inflammation inhibition at a lower effective dose 50 (ED 50 ) than ibuprofen´s. None of the SCIDs endowed with anti-inflammatory activity, showed significant gastrotoxic effects with respect to those displayed by ibuprofen. Based on the experimental results and aided by the theoretical docking approach, it was possible to rationalize how the SCIDs may bind to cyclooxygenase isoforms and helped to explain their reduced gastrotoxicity. The evaluated effects were improved in SCIDs with respect to ibuprofen. Copyright © 2017 Elsevier B.V. All rights reserved.

Intramuscular ketorolac versus oral ibuprofen for pain relief in first-trimester surgical abortion: a randomized clinical trial.

PubMed

Braaten, Kari P; Hurwitz, Shelley; Fortin, Jennifer; Goldberg, Alisa B

2014-02-01

Oral nonsteroidal antiinflammatory medications (NSAIDs) have been shown to reduce pain with first-trimester surgical abortion compared to placebo, but it is unclear if one NSAID is better than another. Some providers administer intramuscular ketorolac, though data regarding its efficacy in abortion are limited. This study was designed to compare oral ibuprofen to intramuscular ketorolac for pain management during first-trimester surgical abortion. This was a randomized, double-blind, controlled trial. Women undergoing first-trimester surgical abortion with local anesthesia were randomized to preprocedural oral ibuprofen, 800 mg given 60-90 min preprocedure, or intramuscular ketorolac, 60 mg given 30-60 min preprocedure. The primary outcome was pain with uterine aspiration on a 21-point, 0-100, numerical rating scale. Secondary outcomes included pain with cervical dilation, postoperative pain and patient satisfaction. Ninety-four women were enrolled; 47 were randomized to ibuprofen and 47 to ketorolac. The groups did not differ with regards to demographics, reproductive history or Depression Anxiety Stress Scale scores. Mean pain scores for suction curettage did not differ between groups (52.3 vs. 56.2, p=.53). There was also no difference in pain with cervical dilation (41.6 vs. 45.4, p=0.48) or postoperative pain (22.3 vs. 15.0 p=.076), though patients in the ketorolac group experienced significantly greater arm pain than those who received a placebo injection (30.4 vs. 15.6, p<.001). Satisfaction with pain control did not differ significantly by group. Intramuscular ketorolac does not offer superior pain control compared to oral ibuprofen for first-trimester surgical abortion. Intramuscular ketorolac does not offer superior pain control over oral ibuprofen during first-trimester surgical abortion, is more expensive and causes patients significant arm discomfort. Its use should therefore be reserved for patients who cannot tolerate oral NSAIDs. © 2014.

Effects of lornoxicam and intravenous ibuprofen on erythrocyte deformability and hepatic and renal blood flow in rats.

PubMed

Arpacı, Hande; Çomu, Faruk Metin; Küçük, Ayşegül; Kösem, Bahadır; Kartal, Seyfi; Şıvgın, Volkan; Turgut, Hüseyin Cihad; Aydın, Muhammed Enes; Koç, Derya Sebile; Arslan, Mustafa

2016-01-01

Change in blood supply is held responsible for anesthesia-related abnormal tissue and organ perfusion. Decreased erythrocyte deformability and increased aggregation may be detected after surgery performed under general anesthesia. It was shown that nonsteroidal anti-inflammatory drugs decrease erythrocyte deformability. Lornoxicam and/or intravenous (iv) ibuprofen are commonly preferred analgesic agents for postoperative pain management. In this study, we aimed to investigate the effects of lornoxicam (2 mg/kg, iv) and ibuprofen (30 mg/kg, iv) on erythrocyte deformability, as well as hepatic and renal blood flows, in male rats. Eighteen male Wistar albino rats were randomly divided into three groups as follows: iv lornoxicam-treated group (Group L), iv ibuprofen-treated group (Group İ), and control group (Group C). Drug administration was carried out by the iv route in all groups except Group C. Hepatic and renal blood flows were studied by laser Doppler, and euthanasia was performed via intra-abdominal blood uptake. Erythrocyte deformability was measured using a constant-flow filtrometry system. Lornoxicam and ibuprofen increased the relative resistance, which is an indicator of erythrocyte deformability, of rats (P=0.016). Comparison of the results from Group L and Group I revealed no statistically significant differences (P=0.694), although the erythrocyte deformability levels in Group L and Group I were statistically higher than the results observed in Group C (P=0.018 and P=0.008, respectively). Hepatic and renal blood flows were significantly lower than the same in Group C. We believe that lornoxicam and ibuprofen may lead to functional disorders related to renal and liver tissue perfusion secondary to both decreased blood flow and erythrocyte deformability. Further studies regarding these issues are thought to be essential.

Effects of low-dose ibuprofen supplementation and resistance training on bone and muscle in postmenopausal women: A randomized controlled trial.

PubMed

Duff, Whitney R D; Kontulainen, Saija A; Candow, Darren G; Gordon, Julianne J; Mason, Riley S; Taylor-Gjevre, Regina; Nair, Bindu; Szafron, Michael; Baxter-Jones, Adam D G; Zello, Gordon A; Chilibeck, Philip D

2016-12-01

To compare the effects of nine months of exercise training and ibuprofen supplementation (given immeditately after exercise sessions) on bone and muscle in postmenopausal women. In a double-blind randomized trial, participants (females: n = 90, mean age 64.8, SD 4.3 years) were assigned (computer generated, double blind) to receive supervised resistance training or stretching 3 days/week, and ibuprofen (400 mg, post-exercise) or placebo (i.e. 4 groups) for 9 months. In this proof-of-concept study the sample size was halved from required 200 identified via 90% power calculation. Baseline and post-intervention testing included: Dual energy x-ray absorptiometry (DXA) for lumbar spine, femoral neck, and total body areal bone mineral density (aBMD); geometry of proximal femur; total body lean tissue and fat mass; predicted 1-repetition maximum muscle strength testing (1RM; biceps curl, hack squat). Exercise training or ibuprofen supplementation had no effects on aBMD of the lumbar spine, femoral neck, and total body. There was a significant exercise × supplement × time interaction for aBMD of Ward's region of the femoral neck (p = 0.015) with post hoc comparison showing a 6% decrease for stretching with placebo vs. a 3% increase for stretching with ibuprofen (p = 0.017). Resistance training increased biceps curl and hack squat strength vs. stretching (22% vs. 4% and 114% vs. 12%, respectively) (p < 0.01) and decreased percent body fat compared to stretching (2% vs. 0%) (p < 0.05). Ibuprofen supplementation provided some benefits to bone when taken independent of exercise training in postmenopausal women. This study provides evidence towards a novel, easily accessible stimulus for enhancing bone health [i.e. ibuprofen].

Quality by design approach for developing chitosan-Ca-alginate microspheres for colon delivery of celecoxib-hydroxypropyl-β-cyclodextrin-PVP complex.

PubMed

Mennini, N; Furlanetto, S; Cirri, M; Mura, P

2012-01-01

The aim of the present work was to develop a new multiparticulate system, designed for colon-specific delivery of celecoxib for both systemic (in chronotherapic treatment of arthritis) and local (in prophylaxis of colon carcinogenesis) therapy. The system simultaneously benefits from ternary complexation with hydroxypropyl-β-cyclodextrin and PVP (polyvinylpyrrolidone), to increase drug solubility, and vectorization in chitosan-Ca-alginate microspheres, to exploit the colon-specific carrier properties of these polymers. Statistical experimental design was employed to investigate the combined effect of four formulation variables, i.e., % of alginate, CaCl₂, and chitosan and time of cross-linking on microsphere entrapment efficiency (EE%) and drug amount released after 4h in colonic medium, considered as the responses to be optimized. Design of experiment was used in the context of Quality by Design, which requires a multivariate approach for understanding the multifactorial relationships among formulation parameters. Doehlert design allowed for defining a design space, which revealed that variations of the considered factors had in most cases an opposite influence on the responses. Desirability function was used to attain simultaneous optimization of both responses. The desired goals were achieved for both systemic and local use of celecoxib. Experimental values obtained from the optimized formulations were in both cases very close to the predicted values, thus confirming the validity of the generated mathematical model. These results demonstrated the effectiveness of the proposed jointed use of drug cyclodextrin complexation and chitosan-Ca-alginate microsphere vectorization, as well as the usefulness of the multivariate approach for the preparation of colon-targeted celecoxib microspheres with optimized properties. Copyright © 2011 Elsevier B.V. All rights reserved.

Quantification of in situ granulation-induced changes in pre-compression, solubility, dose distribution and intrinsic in vitro release characteristics of ibuprofen-cationic dextran conjugate crystanules.

PubMed

Abioye, Amos Olusegun; Kola-Mustapha, Adeola; Chi, George Tangyie; Ilya, Sunday

2014-08-25

The direct effect of intermolecular association between ibuprofen and diethylaminoethyl dextran (Ddex) and the novel 'melt-in situ granulation-crystallization' technique on the solubility, dose distribution, in vitro dissolution kinetics and pre-compression characteristics of the ibuprofen-Ddex conjugate crystanules have been investigated using various mathematical equations and statistical moments. The research intention was to elucidate the mechanisms of ibuprofen solubilization, densification and release from the conjugate crystanules as well as its dose distribution in order to provide fundamental knowledge on important physicochemical, thermodynamic and system-specific parameters which are key indices for the optimization of drug-polymer conjugate design for the delivery of poorly soluble drugs. The process of melt-in situ-granulation-crystallization reduced the solubility slightly compared with pure ibuprofen, however, the ibuprofen-Ddex conjugate crystanules exhibited increased ibuprofen solubility to a maximum of 2.47×10(-1) mM (at 1.25×10(-4) mM Ddex) and 8.72×10(-1) mM (at 6.25×10(-4) mM Ddex) at 25 and 37 °C, respectively. Beyond these concentrations of Ddex ibuprofen solubility decreased steadily due to stronger bond strength of the conjugate crystanules. The enthalpy-entropy compensation plot suggests a dominant entropy-driven mechanism of solubilization. In the same vein, the addition of Ddex increased the rate and extent of in vitro ibuprofen release from the conjugate crystanule to 100% within 168 h at Ddex concentration of 1.56×10(-4) mM, followed by a decrease with Ddex concentration. The conjugate crystanules exhibited controlled and extended-complete release profile which appeared to be dictated by the concentration of the Ddex and its strong affinity for ibuprofen. A comparison of the real experimental with the predicted data using artificial neural network shows excellent correlation between solubility and dissolution profiles (average

Factors associated with efficacy of an ibuprofen/pseudoephedrine combination drug in pharmacy customers with common cold symptoms.

PubMed

Klimek, Ludger; Schumacher, Helmut; Schütt, Tanja; Gräter, Heidemarie; Mueck, Tobias; Michel, Martin C

2017-02-01

The aim of this study was to explore factors affecting efficacy of treatment of common cold symptoms with an over-the-counter ibuprofen/pseudoephedrine combination product. Data from an anonymous survey among 1770 pharmacy customers purchasing the combination product for treatment of own common cold symptoms underwent post-hoc descriptive analysis. Scores of symptoms typically responsive to ibuprofen (headache, pharyngeal pain, joint pain and fever), typically responsive to pseudoephedrine (congested nose, congested sinus and runny nose), considered non-specific (sneezing, fatigue, dry cough, cough with expectoration) and comprising all 11 symptoms were analysed. Multiple regression analysis was applied to explore factors associated with greater reduction in symptom intensity or greater probability of experiencing a symptom reduction of at least 50%. After intake of first dose of medication, typically ibuprofen-sensitive, pseudoephedrine-responsive, non-specific and total symptoms were reduced by 60.0%, 46.3%, 45.4% and 52.8%, respectively. A symptom reduction of at least 50% was reported by 73.6%, 55.1%, 50.9% and 61.6% of participants, respectively. A high baseline score was associated with greater reductions in symptom scores but smaller probability of achieving an improvement of at least 50%. Across both multiple regression approaches, two tablets at first dosing were more effective than one and (except for ibuprofen-sensitive symptoms) starting treatment later than day 2 of the cold was generally less effective. Efficacy of an ibuprofen/pseudoephedrine combination in the treatment of common cold symptoms was dose-dependent and greatest when treatment started within the first 2 days after onset of symptoms. © 2016 The Authors. International Journal of Clinical Practice Published by John Wiley & Sons Ltd.

Enhanced electrochemical degradation of ibuprofen in aqueous solution by PtRu alloy catalyst.

PubMed

Chang, Chiung-Fen; Chen, Tsan-Yao; Chin, Ching-Ju Monica; Kuo, Yu-Tsun

2017-05-01

Electrochemical advanced oxidation processes (EAOPs) regarded as a green technology for aqueous ibuprofen treatment was investigated in this study. Multi-walled carbon nanotubes (MWCNTs), Pt nanoparticles (Pt NPs), and PtRu alloy, of which physicochemical properties were characterized by XRD and X-ray absorption spectroscopy, were used to synthesize three types of cheap and effective anodes based on commercial conductive glass. Furthermore, the operating parameters, such as the current densities, initial concentrations, and solution pH were also investigated. The intermediates determined by a UPLC-Q-TOF/MS system were used to evaluate the possible reaction pathway of ibuprofen (IBU). The results revealed that the usage of MWCNTs and PtRu alloy can effectively reduce the grain size of electrocatalysts and increase the surface activity from the XRD and XANES analysis. The results of CV analysis, degradation and mineralization efficiencies revealed that the EAOPs with PtRu-FTO anode were very effective due to advantages of the higher capacitance, CO tolerance, catalytic ability at less positive voltage and stability. The concentration trend of intermediates indicated that the potential cytotoxic to human caused by 1-(1-hydroxyenthyl)-4-isobutylbenzene was completely eliminated as the reaction time reaches 60 min. Therefore, EAOPs combined with synthesized anodes can be feasibly applied on the electrochemical degradation of ibuprofen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Levels of prostaglandin E metabolite and leukotriene E(4) are increased in the urine of smokers: evidence that celecoxib shunts arachidonic acid into the 5-lipoxygenase pathway.

PubMed

Duffield-Lillico, Anna J; Boyle, Jay O; Zhou, Xi Kathy; Ghosh, Aradhana; Butala, Geera S; Subbaramaiah, Kotha; Newman, Robert A; Morrow, Jason D; Milne, Ginger L; Dannenberg, Andrew J

2009-04-01

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LO) play a role in inflammation and carcinogenesis. Biomarkers that reflect tobacco smoke-induced tissue injury are needed. In this study, levels of urinary prostaglandin E metabolite (PGE-M) and leukotriene E(4) (LTE(4)), biomarkers of the COX and 5-LO pathways, were compared in never smokers, former smokers, and current smokers. The effects of celecoxib, a selective COX-2 inhibitor, on levels of PGE-M and LTE(4) were determined. Baseline levels of PGE-M and LTE(4) were positively associated with smoking status; levels of PGE-M and LTE(4) were higher in current versus never smokers. Treatment with 200 mg celecoxib twice daily for 6 +/- 1 days led to a reduction in urinary PGE-M levels in all groups but exhibited the greatest effect among subjects with high baseline PGE-M levels. Thus, high baseline PGE-M levels in smokers reflected increased COX-2 activity. In individuals with high baseline PGE-M levels, treatment with celecoxib led to a significant increase in levels of urinary LTE(4), an effect that was not found in individuals with low baseline PGE-M levels. In conclusion, increased levels of urinary PGE-M and LTE(4) were found in human smokers, a result that may reflect subclinical lung inflammation. In individuals with high baseline levels of PGE-M (elevated COX-2 activity), celecoxib administration shunted arachidonic acid into the proinflammatory 5-LO pathway. Because 5-LO activity and LTE(4) have been suggested to play a role in cardiovascular disease, these results may help to explain the link between use of COX-2 inhibitors and cardiovascular complications.

Acetaminophen Versus Liquefied Ibuprofen for Control of Pain During Separation in Orthodontic Patients: A Randomized Triple Blinded Clinical Trial.

PubMed

Hosseinzadeh Nik, Tahereh; Shahsavari, Negin; Ghadirian, Hannaneh; Ostad, Seyed Nasser

2016-07-01

The aim of this randomized clinical study was to investigate the effectiveness of acetaminophen 650 mg or liquefied ibuprofen 400 mg in pain control of orthodontic patients during separation with an elastic separator. A total of 101 patients with specific inclusion criteria were divided randomly into three groups (acetaminophen, liquefied ibuprofen, and placebo). They were instructed to take their drugs one hour before separator placement and every six hours afterward (five doses in total). They recorded their discomfort on visual analog scales immediately after separator placement, 2 hours later, 6 hours later, at bedtime, and 24 hours after separator placement. Repeated measure analysis of variance (ANOVA) was used to compare the mean pain scores between the three groups. Data were collected from 89 patients. The pain increased with time in all groups. Pain scores were statistically lower in the analgesic groups compared with the placebo group (P.value<0.001), but no statistically significant difference was found in mean pain scores between the two drug groups (acetaminophen and liquefied ibuprofen) (P.value=1). Acetaminophen and liquefied ibuprofen have similar potential in pain reduction during separation.

Efficacy and tolerability of a new ibuprofen 200mg plaster in patients with acute sports-related traumatic blunt soft tissue injury/contusion.

PubMed

Predel, Hans-Georg; Giannetti, Bruno; Connolly, Mark P; Lewis, Fraser; Bhatt, Aomesh

2018-01-01

Ibuprofen is used for the treatment of non-serious pain. This study assessed the efficacy and safety of a new ibuprofen plaster for the treatment of pain associated with acute sports impact injuries/contusions. In this randomised, double-blind, multi-centre, placebo controlled, parallel group study, adults (n = 130; 18-58 years of age) diagnosed with acute sports-related blunt soft tissue injury/contusion were randomized to receive either ibuprofen 200 mg plaster or placebo plaster. Plasters were administered once daily for five consecutive days. The primary assessment was area under the visual analogue scale (VAS) of pain on movement (POM) over 0 to three days (VAS AUC 0-3d ). Other endpoints included algometry AUC from 0 to three days (AUC 0-3d ) and 0 to five days (AUC 0-5d ), to evaluate improvement of sensitivity at the injured site, and patient and investigator global assessment of efficacy. Safety was monitored throughout the study. The ibuprofen plaster resulted in superior reduction in AUC 0-3d compared with placebo; the Least Squares (LS) mean difference was 662.82 mm*h in favour of the ibuprofen 200mg plaster (P = 0.0011). The greater improvement in VAS AUC of POM was also observed after 12 h, 24 h, and five days of therapy. Tenderness also significantly improved with the ibuprofen plaster compared with placebo; LS mean difference in algometry/tenderness AUC 0-3d was 1.87 N/cm 2 *d and AUC 0-5d was 1.87 N/cm 2 *d (P values ≤0.0004). At all study timepoints, a greater percentage of patients and investigators rated the effectiveness of the ibuprofen 200 mg plaster as good/excellent than the placebo plaster. Treatment-emergent adverse events for the ibuprofen plaster were few (≤1.5%) and were mild in severity. The results of this study indicate 200 mg plaster is effective and safe for the treatment of pain due to acute sports-related traumatic blunt soft tissue injury/contusion in adults.

Adsorption of ibuprofen enantiomers on a chiral stationary phase with a grafted antibiotic eremomycin

NASA Astrophysics Data System (ADS)

Reshetova, E. N.; Asnin, L. D.

2015-02-01

The adsorption of ibuprofen enantiomers on a chiral stationary phase Nautilus-E with a grafted antibiotic eremomycin from aqueous ethanol acetate buffer solutions was studied by chromatography. The ethanol concentration in the mobile phase was varied from 40 to 60 vol %. The adsorption isotherms of both enantiomers had a complex shape characterized by non-Langmuir type curvature and the presence of an inflection point. This is explained by two factors: the energy heterogeneity of the surface of the stationary phase and the dissociation of ibuprofen in the liquid phase. The effect of the system peak on the shape of the chromatograms of the target component was investigated. The temperature effect on the adsorption equilibrium was discussed.

The shortened infusion time of intravenous ibuprofen part 1: a multicenter, open-label, surveillance trial to evaluate safety and efficacy.

PubMed

Bergese, Sergio D; Candiotti, Keith; Ayad, Sabry S; Soghomonyan, Suren; Gan, Tong J

2015-02-01

The main purpose of the study was to determine the safety profile and efficacy of intravenous ibuprofen administered over 5 to 10 minutes for the treatment of pain or fever in hospitalized patients. Current evidence supports the use of intravenous infusions of ibuprofen to control pain and reduce the opioid requirements associated with surgical pain. Current dosing guidelines recommend that the drug be administered over 30 minutes. However, a more rapid infusion might yield additional benefits. The safety profile and efficacy of a shortened infusion time requires additional study. This was a Phase IV multicenter, open-label, surveillance clinical study. Thirteen clinical centers located in the United States enrolled a total of 150 adult hospitalized patients with pain or fever. Patients experiencing pain received 800 mg intravenous ibuprofen infused over 5 to 10 minutes every 6 hours for up to 24 hours (4 doses) and patients experiencing fever received 400 mg intravenous ibuprofen infused over 5 to 10 minutes every 4 hours for up to 24 hours (6 doses). Vital signs, adverse events, and pain scores were assessed. The exclusion criteria included inadequate intravenous access; patients younger than 18 years of age; history of allergy or hypersensitivity to any component of intravenous ibuprofen, aspirin, or other nonsteroid anti-inflammatory drugs; active hemorrhage or clinically significant bleeding; pregnancy or nursing; and patients in the perioperative period in the setting of coronary artery bypass graft surgery. Adverse events were reported for 43 of 150 patients (29%). The most common adverse events experienced by patients were infusion site pain in 22 of 150 patients (15%) and flatulence (8 of 150 [5%]). Four patients (3%) discontinued the study drug due to infusion-site pain. In the patients experiencing fever, temperature decreased from baseline over 4 hours (mean [SD] reduction of 1.5 [1.25]°F). In patients experiencing pain, patient-reported visual analog

Administration of a co-crystal of tramadol and celecoxib in a 1:1 molecular ratio produces synergistic antinociceptive effects in a postoperative pain model in rats.

PubMed

Merlos, Manuel; Portillo-Salido, Enrique; Brenchat, Alex; Aubel, Bertrand; Buxens, Jordi; Fisas, Angels; Codony, Xavier; Romero, Luz; Zamanillo, Daniel; Vela, José Miguel

2018-06-19

Drug combination for the treatment of pain is common clinical practice. Co-crystal of Tramadol-Celecoxib (CTC) consists of two active pharmaceutical ingredients (APIs), namely the atypical opioid tramadol and the preferential cyclooxygenase-2 inhibitor celecoxib, at a 1:1 molecular ratio. In this study, a non-formulated 'raw' form of CTC administered in suspension (referred to as ctc susp ) was compared with both tramadol and celecoxib alone in a rat plantar incision postoperative pain model. For comparison, the strong opioids morphine and oxycodone, and a tramadol plus acetaminophen combination at a molecular ratio of 1:17 were also tested. Isobolographic analyses showed that ctc susp exerted synergistic mechanical antiallodynic (experimental ED 50 =2.0±0.5mg/kg, i.p.; theoretical ED 50 =3.8±0.4mg/kg, i.p.) and thermal (experimental ED 50 =2.3±0.5mg/kg, i.p.; theoretical ED 50 =9.8±0.8mg/kg, i.p.) antihyperalgesic effects in the postoperative pain model. In contrast, the tramadol and acetaminophen combination showed antagonistic effects on both mechanical allodynia and thermal hyperalgesia. No synergies between tramadol and celecoxib on locomotor activity, motor coordination, ulceration potential and gastrointestinal transit were observed after the administration of ctc susp . Overall, rat efficacy and safety data revealed that ctc susp provided synergistic analgesic effects compared with each API alone, without enhancing adverse effects. Moreover, ctc susp showed similar efficacy but improved safety ratio (80, measured as gastrointestinal transit vs postoperative pain ED 50 ratios) compared with the strong opioids morphine (2.5) and oxycodone (5.8). The overall in vivo profile of ctc susp supports the further investigation of CTC in the clinical management of moderate-to-severe acute pain as an alternative to strong opioids. Copyright © 2018. Published by Elsevier B.V.

Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial

PubMed Central

Bleidorn, Jutta; Kochen, Michael M; Schmiemann, Guido; Wegscheider, Karl; Hummers-Pradier, Eva

2015-01-01

Study question Can treatment of the symptoms of uncomplicated urinary tract infection (UTI) with ibuprofen reduce the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications? Methods Women aged 18-65 with typical symptoms of UTI and without risk factors or complications were recruited in 42 German general practices and randomly assigned to treatment with a single dose of fosfomycin 3 g (n=246; 243 analysed) or ibuprofen 3×400 mg (n=248; 241 analysed) for three days (and the respective placebo dummies in both groups). In both groups additional antibiotic treatment was subsequently prescribed as necessary for persistent, worsening, or recurrent symptoms. The primary endpoints were the number of all courses of antibiotic treatment on days 0-28 (for UTI or other conditions) and burden of symptoms on days 0-7. The symptom score included dysuria, frequency/urgency, and low abdominal pain. Study answer and limitations The 248 women in the ibuprofen group received significantly fewer course of antibiotics, had a significantly higher total burden of symptoms, and more had pyelonephritis. Four serious adverse events occurred that lead to hospital referrals; one of these was potentially related to the trial drug. Results have to be interpreted carefully as they might apply to women with mild to moderate symptoms rather than to all those with an uncomplicated UTI. What this paper adds Two thirds of women with uncomplicated UTI treated symptomatically with ibuprofen recovered without any antibiotics. Initial symptomatic treatment is a possible approach to be discussed with women willing to avoid immediate antibiotics and to accept a somewhat higher burden of symptoms. Funding, competing interests, data sharing German Federal Ministry of Education and Research (BMBF) No 01KG1105. Patient level data are available from the corresponding author. Patient consent was not obtained but the data are anonymised and risk of

Prophylactic compared with therapeutic ibuprofen analgesia in first-trimester medical abortion: a randomized controlled trial.

PubMed

Raymond, Elizabeth G; Weaver, Mark A; Louie, Karmen S; Dean, Gillian; Porsch, Lauren; Lichtenberg, E Steve; Ali, Rose; Arnesen, Michelle

2013-09-01

To compare the effectiveness of two oral analgesic regimens in first-trimester medical abortion. We randomly assigned 250 participants undergoing first-trimester abortion with mifepristone and misoprostol at three clinics to two ibuprofen regimens: therapeutic (800 mg every 4-6 hours as needed for pain) or prophylactic (800 mg starting 1 hour before the misoprostol dose, then every 4-6 hours for 48 hours regardless of pain, then as needed). We asked each participant to record her maximum pain on a scale of 0-10 daily thereafter. Of participants assigned to the prophylactic and therapeutic regimens, 111 of 123 (90%) and 117 of 127 (92%), respectively, provided follow-up data. More than 80% of the participants in each group complied with their assigned treatment. Participants in the prophylactic group used substantially more ibuprofen than those in the therapeutic group (median of nine and four tablets, respectively). The mean maximum pain score was 7.1 in the prophylactic group and 7.3 in the therapeutic group (standard deviations 2.5 and 2.2, respectively); the difference was not statistically significant (P=.87, adjusted for site). Duration of pain, verbal pain ratings reported at follow-up, and use of other analgesics did not differ significantly by group (all P>.05). No significant benefit of the prophylactic regimen was apparent in any population subgroup. Abortion failure and ibuprofen side effects in the two groups were similar. We found no evidence that prophylactic administration of ibuprofen reduces pain severity or duration in first-trimester medical abortion. The average pain severity experienced by participants using both regimens was high. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01457521. I.

Ibuprofen induces reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA uptake in severe epithelial breast hyperplasia without atypia.

PubMed

Papantoniou, Vassilios; Tsaroucha, Angeliki; Valsamaki, Pipitsa; Tsiouris, Spyridon; Sotiropoulou, Evangelia; Karianos, Theodore; Marinopoulos, Spyridon; Fothiadaki, Athina; Sotiropoulou, Maria; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Dimitrakakis, Konstantinos; Antsaklis, Aris

2010-10-01

The purpose of this study was to investigate if ibuprofen intake can influence mammary uptake of the proliferation-seeking radiotracer technetium 99m-pentavalent dimercaptosuccinic acid (99mTc-(V)DMSA) in women with severe epithelial and atypical epithelial breast hyperplasia. Eight patients with histologically confirmed severe epithelial breast hyperplasia with (n  =  4) and without atypia (n  =  4) were submitted prospectively to 99mTc-(V)DMSA scintimammography before and after a 4-week course of 400 mg ibuprofen daily oral intake. Lesion to background ratios 60 minutes postinjection were calculated and compared (t-test) before and after ibuprofen administration. Prior to ibuprofen, the patients with severe epithelial hyperplasia displayed a significantly higher 99mTc-(V)DMSA uptake ratio compared to those with atypical epithelial hyperplasia (2.40 ± 0.32 vs 1.67 ± 0.09, respectively; p  =  .003). They also exhibited a more substantial percent decline in tracer uptake postibuprofen compared to women with atypical epithelial hyperplasia (62.0 ± 7.1 vs 15.0 ± 0.2, respectively; p  =  .001). Ibuprofen induces significant uptake reduction of the proliferation-seeking radiotracer 99mTc-(V)DMSA in severe epithelial breast hyperplasia without atypia. This agent could therefore constitute a potential imaging tool for monitoring chemoprophylaxis effectiveness in women at the early stages of malignant transformation.

Design and Concept of Polyzwitterionic Copolymer Microgel Drug Delivery Systems In Situ Loaded with Non-steroidal Anti-inflammatory Ibuprofen.

PubMed

Kostova, Bistra; Kamenska, Elena; Georgieva, Dilyana; Balashev, Konstantin; Rachev, Dimitar; Georgiev, George

2017-01-01

Nowadays, the modern pharmaceutical investigations are directed toward obtaining of new polymer micro- and nano-sized drug delivery carriers. In this respect, the use of hydrogel carriers based on polyzwitterions (PZIs) is an opportunity in the preparation of polymer drug delivery systems with desired characteristics. This paper describes the synthesis and characterization of micro-structured p(VA-co-DMAPS) systems with different compositions in situ loaded with Ibuprofen by emulsifier-free emulsion copolymerization (EEC) in water. The mean size of the prepared microparticles was measured by SEM and particles have been visualized by AFM. The inclusion of Ibuprofen in the polyzwitterionic copolymer microgel systems was established by using DSC. In vitro drug release experiments were carried out in order to estimate the ability of the obtained microgels to modify the release of water-insoluble Ibuprofen.

Comparison of the effects of treatment with celecoxib, loxoprofen, and acetaminophen on postoperative acute pain after arthroscopic knee surgery: A randomized, parallel-group trial.

PubMed

Onda, Akira; Ogoshi, Atsuko; Itoh, Mieko; Nakagawa, Tomoyuki; Kimura, Masashi

2016-03-01

Selective cyclooxygenase-2 (COX-2) inhibitors, conventional non-selective nonsteroidal anti-inflammatory drugs (NSAIDs), and acetaminophen have been adopted for the relief of mild to moderate acute and chronic pain. However, it remains unclarified whether the therapeutic differences in pain sensation exist among these agents. The aim of this study was to compare the efficacy of different types of analgesic agents for postoperative acute pain management. A single-center, randomized, controlled study was performed in consecutive patients who underwent the second-look procedure with removal of internal fixation after anterior cruciate ligament reconstruction or arthroscopic meniscal repair/meniscectomy. Celecoxib (400 mg for the first dose and then 200 mg), loxoprofen (60 mg), or acetaminophen (600 mg) was orally administered from postoperative 3 h. The pain intensity on a 100-mm VAS scale and subjective assessment of therapeutic pain-relief were compared among these three treatment groups until postoperative 2 days. The acquired data were analyzed according to the per-protocol analysis principle. A total of 432 patients were screened, and 160 were enrolled. The VAS score tended to decrease over time in all groups. There was a significant improvement in the pain score both at rest and on movement, and subjective impression in the celecoxib-treated group compared with acetaminophen at postoperative 2 days. On the other hand, loxoprofen resulted in the benefit only in the pain score at rest in comparison with acetaminophen. Any comparisons between celecoxib and loxoprofen showed insignificant differences throughout observations. No adverse effects were confirmed in each group. These obtained findings in our dose setting conditions suggest that celecoxib and loxoprofen treatments were superior to acetaminophen in pain-relief, though the superiority of loxoprofen over acetaminophen was modest. Overall, selective COX-2 inhibitors including conventional NSAIDs seem to

Association of High-Dose Ibuprofen Use, Lung Function Decline, and Long-Term Survival in Children with Cystic Fibrosis.

PubMed

Konstan, Michael W; VanDevanter, Donald R; Sawicki, Gregory S; Pasta, David J; Foreman, Aimee J; Neiman, Evgueni A; Morgan, Wayne J

2018-04-01

Cystic fibrosis deaths result primarily from lung function loss, so chronic respiratory therapies, intended to preserve lung function, are cornerstones of cystic fibrosis care. Although treatment-associated reduction in rate of lung function loss should ultimately improve cystic fibrosis survival, no such relationship has been described for any chronic cystic fibrosis therapy. In part, this is because the ages of most rapid lung function decline-early adolescence-precede the median age of cystic fibrosis deaths by more than a decade. To study associations of high-dose ibuprofen treatment with the rate of forced expiratory volume in 1 second decline and mortality among children followed in the Epidemiologic Study of Cystic Fibrosis and subsequently in the U.S. Cystic Fibrosis Foundation Patient Registry. We performed a matched cohort study using data from Epidemiologic Study of Cystic Fibrosis. Exposure was defined as high-dose ibuprofen use reported at ≥80% of encounters over 2 years. Unexposed children were matched to exposed children 5:1 using propensity scores on the basis of demographic, clinical, and treatment covariates. The rate of decline of percent predicted forced expiratory volume in 1 second during the 2-year follow-up period was estimated by mixed-effects modeling with random slopes and intercepts. Survival over 16 follow-up years in the U.S. Cystic Fibrosis Foundation Patient Registry was compared between treatment groups by using proportional hazards modeling controlling for matching and covariates. We included 775 high-dose ibuprofen users and 3,665 nonusers who were well matched on demographic, clinical, and treatment variables. High-dose ibuprofen users declined on average 1.10 percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 0.51, 1.69) during the 2-year treatment period, whereas nonusers declined at a rate of 1.76% percent predicted forced expiratory volume in 1 second/yr (95% confidence interval; 1.48, 2

Renal stress and kidney injury biomarkers in response to endurance cycling in the heat with and without ibuprofen.

PubMed

McDermott, Brendon P; Smith, Cody R; Butts, Cory L; Caldwell, Aaron R; Lee, Elaine C; Vingren, Jakob L; Munoz, Colleen X; Kunces, Laura J; Williamson, Keith; Ganio, Matthew S; Armstrong, Lawrence E

2018-05-16

Exercise, especially in the heat, can contribute to acute kidney injury, which can expedite chronic kidney disease onset. The additional stress of ibuprofen use is hypothesized to increase renal stress. To observe the effects of endurance cycling in the heat on renal function. Secondarily, we investigated the effect of ibuprofen ingestion on kidney stress. Randomized, placebo controlled and observational methods were utilized. Forty cyclists (52±9y, 21.7±6.5% body fat) volunteered and completed an endurance cycling event (5.7±1.2h) in the heat (33.2±5.0°C, 38.4±10.7% RH). Thirty-five participants were randomized to ingest a placebo (n=17) or 600mg ibuprofen (n=18) pre-event. A blood sample was drawn before and following the event. Serum creatinine was assessed by colorimetric assay. An ELISA was used to measure serum neutrophil gelatinase-associated lipocalin. Fractional excretion of sodium was calculated after urinary and serum electrolyte analyses. Placebo versus ibuprofen groups contributed no significant difference in any variable (p>0.05). Serum creatinine significantly increased from pre- (0.52±0.14mg/dL) to post-event (0.88±0.21mg/dL; p<0.001). Serum neutrophil gelatinase-associated lipocalin significantly increased (pre: 68.51±17.54ng/mL; post: 139.12±36.52ng/mL; p<0.001) and fractional excretion of sodium was significantly reduced from pre- (0.52±0.24%) to post-event (0.27±0.18%; p<0.001). Changes in renal biomarkers suggest mild acute kidney injury and reduced kidney function during a single bout of endurance cycling in the heat, without influence from moderate ibuprofen ingestion. Copyright © 2018 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Efficacy and safety of Curcuma domestica extracts compared with ibuprofen in patients with knee osteoarthritis: a multicenter study

PubMed Central

Kuptniratsaikul, Vilai; Dajpratham, Piyapat; Taechaarpornkul, Wirat; Buntragulpoontawee, Montana; Lukkanapichonchut, Pranee; Chootip, Chirawan; Saengsuwan, Jittima; Tantayakom, Kesthamrong; Laongpech, Supphalak

2014-01-01

Objective To determine the efficacy and safety of Curcuma domestica extracts in pain reduction and functional improvement. Methods 367 primary knee osteoarthritis patients with a pain score of 5 or higher were randomized to receive ibuprofen 1,200 mg/day or C. domestica extracts 1,500 mg/day for 4 weeks. The main outcomes were Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total, WOMAC pain, WOMAC stiffness, and WOMAC function scores. Adverse events (AEs) were also recorded. Results 185 and 182 patients were randomly assigned into C. domestica extracts and ibuprofen groups, respectively. The baseline characteristics were no different between groups. The mean of all WOMAC scores at weeks 0, 2, and 4 showed significant improvement when compared with the baseline in both groups. After using the noninferiority test, the mean difference (95% confidence interval) of WOMAC total, WOMAC pain, and WOMAC function scores at week 4 adjusted by values at week 0 of C. domestica extracts were noninferior to those for the ibuprofen group (P=0.010, P=0.018, and P=0.010, respectively), except for the WOMAC stiffness subscale, which showed a trend toward significance (P=0.060). The number of patients who developed AEs was no different between groups. However, the number of events of abdominal pain/discomfort was significantly higher in the ibuprofen group than that in the C. domestica extracts group (P=0.046). Most subjects (96%–97%) were satisfied with the treatment, and two-thirds rated themselves as improved in a global assessment. Conclusion C. domestica extracts are as effective as ibuprofen for the treatment of knee osteoarthritis. The side effect profile was similar but with fewer gastrointestinal AE reports in the C. domestica extracts group. PMID:24672232

The effect of food on gastrointestinal (GI) transit of sustained-release ibuprofen tablets as evaluated by gamma scintigraphy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borin, M.T.; Khare, S.; Beihn, R.M.

1990-03-01

The GI transit of radiolabeled sustained-release ibuprofen 800-mg tablets in eight healthy, fed volunteers was monitored using external gamma scintigraphy. Ibuprofen serum concentrations were determined from blood samples drawn over 36 hr following dosing. Sustained-release ibuprofen tablets containing 0.18% of 170Er2O3 (greater than 96% 170Er) in the bulk formulation were manufactured under pilot-scale conditions and were radiolabeled utilizing a neutron activation procedure which converted stable 170Er to radioactive 171Er (t1/2 = 7.5 hr). At the time of dosing, each tablet contained 50 mu Ci of 171Er. Dosage form position were reported at various time intervals. In five subjects the sustained-releasemore » tablet remained in the stomach and eroded slowly over 7-12 hr, resulting in gradual increases in small bowel radioactivity. In the remaining three subjects, the intact tablet was ejected from the stomach and a gastric residence time of approximately 4 hr was measured. This is in marked contrast to a previous study conducted in fasted volunteers in which gastric retention time ranged from 10 to 60 min. Differences in GI transit between fed and fasted volunteers had little effect on ibuprofen bioavailability. AUC and Tmax were unaltered and Cmax was increased by 24%, which is in agreement with results from a previous, crossover-design food effect study.« less

Pre-emptive effect of ibuprofen versus placebo on pain relief and success rates of medical abortion: a double-blind, randomized, controlled study.

PubMed

Avraham, Sarit; Gat, Itai; Duvdevani, Nir-Ram; Haas, Jigal; Frenkel, Yair; Seidman, Daniel S

2012-03-01

To determine the efficacy of pre-emptive administration of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen vs. a placebo on pain relief during medical abortion and to evaluate whether NSAIDs interfere with the action of misoprostol. Prospective, double-blind, randomized, controlled study. University-affiliated tertiary hospital. Sixty-one women who underwent first-trimester termination of pregnancy. Patients received 600 mg mifepristone orally, followed by 400 μg oral misoprostol 2 days later. They were randomized to receive pre-emptively two tablets of 400 mg ibuprofen orally or a placebo, when taking the misoprostol. The patients completed a questionnaire about side effects and pain score and returned for an ultrasound follow-up examination 10-14 days after the medical abortion. Significant pain, assessed by the need for additional analgesia, and failure rates, defined by a need for surgical intervention. Pre-emptive ibuprofen treatment was found to be more effective than a placebo in pain prevention, as determined by a significantly lower need for additional analgesia: 11 of 29 (38%) vs. 25 of 32 (78%), respectively. Treatment failure rate was not statistically different between the ibuprofen and placebo groups: 4 of 28 (14.2%) vs. 3 of 31 (9.7%), respectively. History of menstrual pain was predictive for the need of additional analgesia. Pre-emptive use of ibuprofen had a statistically significant beneficial effect on the need for pain relief during a mifepristone and misoprostol regimen for medical abortion. Ibuprofen did not adversely affect the outcome of medical abortion. NCT00997074. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Aspirin, Ibuprofen, and the Risk for Colorectal Cancer in Lynch Syndrome

PubMed Central

Ait Ouakrim, Driss; Dashti, Seyedeh Ghazaleh; Chau, Rowena; Buchanan, Daniel D.; Clendenning, Mark; Rosty, Christophe; Winship, Ingrid M.; Young, Joanne P.; Giles, Graham G.; Leggett, Barbara; Macrae, Finlay A.; Ahnen, Dennis J.; Casey, Graham; Gallinger, Steven; Haile, Robert W.; Le Marchand, Loïc; Thibodeau, Stephen N.; Lindor, Noralane M.; Newcomb, Polly A.; Potter, John D.; Baron, John A.; Hopper, John L.; Jenkins, Mark A.

2015-01-01

Background: Inheritance of a germline mutation in one of the DNA mismatch repair (MMR) genes MLH1, MSH2, MSH6, and PMS2 causes a high risk of colorectal and other cancers (Lynch Syndrome). Use of aspirin has been shown to be associated with a reduced risk of colorectal cancer for the general population as well as for MMR gene mutation carriers. The aim of this study was to determine whether use of aspirin and ibuprofen in a nontrial setting is associated with the risk of colorectal cancer risk for MMR gene mutation carriers. Methods: We included 1858 participants in the Colon Cancer Family Registry who had been found to have a pathogenic germline mutation in a MMR gene (carriers). We used weighted Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. Results: A total of 714 carriers (38%) were diagnosed with colorectal cancer at a mean age of 42.4 (standard deviation 10.6) years. A reduced risk of colorectal cancer was associated with aspirin use (for 1 month to 4.9 years: HR = 0.49, 95% CI = 0.27 to 0.90, P = .02; for ≥5 years: HR = 0.25, 95% CI = 0.10 to 0.62, P = .003) and ibuprofen use (for 1 month to 4.9 years: HR = 0.38, 95% CI = 0.18 to 0.79, P = .009; for ≥5 years: HR = 0.26, 95% CI = 0.10 to 0.69, P = .007), compared with less than one month of use. Conclusion: Our results provide additional evidence that, for MMR gene mutation carriers, use of aspirin and ibuprofen might be effective in reducing their high risk of colorectal cancer. PMID:26109217

Formulation, and physical, in vitro and ex vivo evaluation of transdermal ibuprofen hydrogels containing turpentine oil as penetration enhancer.

PubMed

Khan, N R; Khan, G M; Wahab, A; Khan, A R; Hussain, A; Nawaz, A; Akhlaq, M

2011-11-01

The aim of the present study was to investigate the transdermal permeation enhancing capability of turpentine oil for ibuprofen from hydrogels. Ibuprofen 1% w/v hydrogels were developed with carboxypolymethylene with and without turpentine oil. Turpentine oil was incorporated in increasing concentrations, i.e. 0.5, 1, 1.5, 2, 2.5 and 3% of the total gel formulation, and its permeation enhancing effect was examined. Gels were examined physically for pH, viscosity, spreadability, extrudability, smoothness and appearance. To study the in vitro and ex vivo permeation potential of formulated gels, permeation studies were performed with a Franz diffusion cell using cellulose membrane and excised rabbit abdominal skin. Ibuprofen hydrogel with 3% turpentine oil showed a maximum flux of 10.87 mg/cm2/h across artificial skin and 17.26 mg/cm2/h across rabbit abdominal skin.

Photodegradation of ibuprofen under UV-Vis irradiation: mechanism and toxicity of photolysis products.

PubMed

Li, Fu Hua; Yao, Kun; Lv, Wen Ying; Liu, Guo Guang; Chen, Ping; Huang, Hao Ping; Kang, Ya Pu

2015-04-01

The photodegradation of ibuprofen (IBP) in aqueous media was studied in this paper. The degradation mechanism, the reaction kinetics and toxicity of the photolysis products of IBP under UV-Vis irradiation were investigated by dissolved oxygen experiments, quenching experiments of reactive oxygen species (ROS), and toxicity evaluation utilizing Vibrio fischeri. The results demonstrated that the IBP degradation process could be fitted by the pseudo first-order kinetics model. The degradation of IBP by UV-Vis irradiation included direct photolysis and self-sensitization via ROS. The presence of dissolved oxygen inhibited the photodegradation of IBP, which indicated that direct photolysis was more rapid than the self-sensitization. The contribution rates of ·OH and (1)O2 were 21.8 % and 38.6 % in self-sensitization, respectively. Ibuprofen generated a number of intermediate products that were more toxic than the base compound during photodegradation.

Synthesis, anti-inflammatory, bactericidal activities and docking studies of novel 1,2,3-triazoles derived from ibuprofen using click chemistry.

PubMed

Angajala, Kishore Kumar; Vianala, Sunitha; Macha, Ramesh; Raghavender, M; Thupurani, Murali Krishna; Pathi, P J

2016-01-01

Nonsteroidal anti-inflammatory drugs are of vast therapeutic benefit in the treatment of different types of inflammatory conditions. 1,2,3-Triazoles and their derivatives have a wide range of applications as anti-bacterial, anti-fungal, anti-tubercular, cytostatic, anti-HIV, anti-allergic, anti-neoplastic and anti-inflammatory (AI) agents. Considering the individual biological and medicinal importance of ibuprofen and 1,2,3-triazoles, we wanted to explore novel chemical entities based on ibuprofen and triazole moieties towards their biological significance. Click chemistry has utilized as an ideal strategy to prepare novel ibuprofen-based 1,4-disubstituted 1,2,3-triazole containing molecules. These compounds were screened for their in vivo AI activity, among all the synthesized analogues 13o was shown potent effect than the reference AI drug ibuprofen at the same concentration (10 mg/kg body weight). Compounds 13l, 13g, 13c, 13k, 13i, 13n, 13m and 13j were shown significant AI activity. These triazole analogues were also screened for their bactericidal profile. Compounds 13c, 13i, 13l and 13o exhibited considerable bactericidal activity against gram positive and gram negative strains. In addition to this, molecular docking studies were also carried out into cyclooxygenase-2 active site to predict the affinity and orientation of these novel compounds (13a-q). In summary, we have designed and synthesized 1,2,3-triazole analogues of ibuprofen in good yields using Click chemistry approach. AI and bactericidal activities of these compounds were evaluated and shown remarkable results.

Oral paracetamol and/or ibuprofen for treating pain after soft tissue injuries: Single centre double-blind, randomised controlled clinical trial

PubMed Central

Lo, Ronson S. L.; Leung, Yuk Ki; Leung, Ling Yan; Man, S. Y.; Woo, W. K.; Cattermole, Giles N.; Rainer, Timothy H.

2018-01-01

Background Soft tissue injuries commonly present to the emergency department (ED), often with acute pain. They cause significant suffering and morbidity if not adequately treated. Paracetamol and ibuprofen are commonly used analgesics, but it remains unknown if either one or the combination of both is superior for pain control. Objectives To investigate the analgesic effect of paracetamol, ibuprofen and the combination of both in the treatment of soft tissue injury in an ED, and the side effect profile of these drugs. Methods Double-blind, double dummy, placebo-controlled randomised controlled trial. 782 adult patients presenting with soft tissue injury without obvious fractures attending the ED of a university hospital in the New Territories of Hong Kong were recruited. Patients were randomised using a random number table into three parallel arms of paracetamol only, ibuprofen only and a combination of paracetamol and ibuprofen in a 1:1:1 ratio. The primary outcome measure was pain score at rest and on activity in the first 2 hours and first 3 days. Data was analysed on an intention to treat basis. Results There was no statistically significant difference in pain score in the initial two hours between the three groups, and no clinically significant difference in pain score in the first three days. Conclusion There was no difference in analgesic effects or side effects observed using oral paracetamol, ibuprofen or a combination of both in patients with mild to moderate pain after soft tissue injuries attending the ED. Trial registration The study is registered with ClinicalTrials.gov (no. NCT00528658). PMID:29408866

Impact of in situ granulation and temperature quenching on crystal habit and micromeritic properties of ibuprofen-cationic dextran conjugate crystanules.

PubMed

Abioye, Amos Olusegun; Kola-Mustapha, Adeola; Ruparelia, Ketan

2014-02-28

Ibuprofen was recrystallized in the presence of aqueous solution of cationic dextran derivative, Diethylaminoethyl Dextran (Ddex) using the melt-in situ granulation-crystallization technique in order to produce a stable amorphous ibuprofen-Ddex conjugates with improved morphological, micromeritic and thermo-analytical characteristics without the use of organic solvent. Ddex was used in this study because of its ability to form conjugates with various drug molecules and enhance their physicochemical characteristics and therapeutic activities. Cationic dextrans are also biocompatible and biodegradable. Mechanism of conjugation as well as the impact of conjugation on the ibuprofen crystal habit was investigated. Gaussian type normal particle size distribution was obtained and the size of the crystals in the crystanule conjugates decreased steadily, with increasing concentration of Ddex, to a minimum of 480 nm (440-folds reduction, p<0.05, n=20) at Ddex molar concentration of 0.01 mM. FT-IR spectra showed electrostatic interaction and hydrogen bonding between ibuprofen and Ddex which was confirmed with the (1)H NMR and (13)C NMR spectra. DSC curves exhibited single peaks from the binary ibuprofen-Ddex conjugate crystanules suggesting compatibility and formation of an eutectic product. The conjugate crystanules showed broad and diffuse endothermic peaks with a glass transition temperature (T(g)) of 58.3 and 59.14°C at Ddex molar concentrations of 1.56 × 10(-4) and 3.125 × 10(-4)mM respectively confirming the existence of ibuprofen-Ddex crystanule conjugates in amorphous state. Higher concentrations of Ddex decreased T(g) steadily. TGA curves showed first order degradation at low molar concentrations of Ddex up to 3.125 × 10(-4)mM which coincides with the critical granular concentration of the crystanules while higher concentrations exhibited second order degradation profile. This study provides the basis for the development of stable amorphous drug

Determination of ibuprofen, naproxen and diclofenac in aqueous samples using a multi-template molecularly imprinted polymer as selective adsorbent for solid-phase extraction.

PubMed

Madikizela, Lawrence Mzukisi; Chimuka, Luke

2016-09-05

This study describes the application of multi-template molecularly imprinted polymer (MIP) as selective sorbent in the solid-phase extraction (SPE) of naproxen, ibuprofen and diclofenac from wastewater and river water. MIP was synthesized at 70°C by employing naproxen, ibuprofen and diclofenac as multi-templates, ethylene glycol dimethacrylate, 2-vinyl pyridine and toluene as cross-linker, functional monomer and porogen, respectively. Wastewater and river water samples (pH 2.5) were percolated through SPE cartridge packed with 50mg of the MIP. The cartridge was washed with 2mL of methanol-water 10:90% (v:v) prior to elution with 2mL of acetic acid-acetonitrile 20:80% (v:v). Quantification of eluted compounds was performed with high performance liquid chromatography equipped with photo diode array detection. The detection limits were 0.15, 1.00 and 0.63μgL(-1) for naproxen, ibuprofen and diclofenac, respectively. Recoveries for naproxen, ibuprofen and diclofenac in deionized water spiked at 5 and 50μgL(-1) were greater than 80%. Ibuprofen was the most frequently detected compound with maximum concentrations of 221, 67.9 and 11.4μgL(-1) in wastewater influent, effluent and river water, respectively. Copyright © 2016 Elsevier B.V. All rights reserved.

Alternating Acetaminophen and Ibuprofen versus Monotherapies in Improvements of Distress and Reducing Refractory Fever in Febrile Children: A Randomized Controlled Trial.

PubMed

Luo, Shuanghong; Ran, Mengdong; Luo, Qiuhong; Shu, Min; Guo, Qin; Zhu, Yu; Xie, Xiaoping; Zhang, Chongfan; Wan, Chaomin

2017-10-01

No evidence can be found in the medical literature about the efficacy of alternating acetaminophen and ibuprofen treatment in children with refractory fever. Our objective was to assess the effect of alternating acetaminophen and ibuprofen therapy on distress and refractory fever compared with acetaminophen or ibuprofen as monotherapy in febrile children. A total of 474 febrile children with axillary temperature ≥38.5 °C and fever history ≤3 days in a tertiary hospital were randomly assigned to receive either (1) alternating acetaminophen and ibuprofen (acetaminophen 10 mg/kg per dose with shortest interval of 4 h and ibuprofen 10 mg/kg per dose with shortest interval of 6 h and the shortest interval between acetaminophen and ibuprofen ≥2 h; n = 158), (2) acetaminophen monotherapy (10 mg/kg per dose with shortest interval of 4 h; n = 158), or (3) ibuprofen monotherapy (10 mg/kg per dose with shortest interval of 6 h; n = 158). The mean Non-Communicating Children's Pain Checklist (NCCPC) score was measured every 4 h, and axillary temperatures were measured every 2 h. In total, 471 children were included in an intention-to-treat analysis. No significant clinical or statistical difference was found in mean NCCPC score or temperature during the 24-h treatment period in all febrile children across the three groups. Although the proportion of children with refractory fever for 4 h and 6 h was significantly lower in the alternating group than in the monotherapy groups (4 h: 11.54% vs. 26.58% vs. 21.66%, respectively [p = 0.003]; 6 h: 3.85% vs. 10.13% vs. 17.83%, respectively [p < 0.001]), the mean NCCPC score of children with refractory fever for 4 or 6 h was not lower than those in either of the monotherapy groups. The number of patients who developed persistent high body temperature was consistent across all study groups. Alternating acetaminophen and ibuprofen can reduce the proportion of children with refractory fever, but if one cycle

Synthesis and Study of Analgesic and Anti-inflammatory Activities of Amide Derivatives of Ibuprofen.

PubMed

Ahmadi, Abbas; Khalili, Mohsen; Olama, Zahra; Karami, Shirin; Nahri-Niknafs, Babak

2017-01-01

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs worldwide and represent a mainstay in the therapy of acute and chronic pain and inflammation. The traditional NSAIDs like ibuprofen (I) contain free carboxylic acid group which can produce gastrointestinal (GI) damage for long-term use. In order to obtain the novel NSAIDs with less side effects; carboxylic acid moiety has been modified into various amide groups which is the most active area of research in this family. In this research, synthesis of various pharmacological heterocyclic amides of ibuprofen is described. All the new compounds were tested for their analgesic and anti-inflammatory activities in mice and compared with standard (Ibuprofen) and control (saline) groups. The results revealed that all the synthesized compounds (III-VI) exhibited more analgesic and anti-inflammatory activities in tail immersion (as a model of acute thermal pain), formalin (as a model of acute chemical and chronic pain) and paw edema (as a model of acute inflammation) tests when compared with standard and control animals. These pharmacological activities were significant for VI compared to other new compounds (III-V) which may be concern to more effective role of morpholin for the reduction of pain and inflammation compared to other used heterocyclic amines. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmacokinetics and tolerability of intravenous ibuprofen injection in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study
.

PubMed

Zhou, Huili; Xu, Wei; Wu, Guolan; Wu, Lihua; Shentu, Jianzhong; Pan, Zhengfei; Hu, Shuai; Liu, Yang

2016-11-01

Recently a formulation of intravenous (IV) ibuprofen was developed in China for management of mild to moderate pain in patients who could not take oral medications or where intravenous administration was preferable. The aim of this study was to evaluate the pharmacokinetic properties and tolerability of single and multiple doses of ibuprofen injection in healthy Chinese volunteers. This open-label, single- and multiple-dose study was conducted in healthy Chinese volunteers. In the single-dose phase, subjects were randomized to receive a single dose of ibuprofen injection 0.2, 0.4, or 0.8 g administered as a 30-minute IV infusion with a 1-week washout between periods. Blood samples were collected at regular intervals from 0 to 12.5 hours after drug administration and were analyzed using a validated LC-MS/MS method. In the multiple-dose phase, subjects received 0.4 g ibuprofen every 6 hours for 9 doses. Blood samples were obtained before the 7^th, 8^th, and 9^th administration to determine the C_min at steady state; on the 9^th intravenous administration, blood samples were also collected for 12.5 hours after drug administration. Pharmacokinetic parameters were estimated using a noncompartmental model. Tolerability was determined using clinical evaluation and monitoring of adverse events (AEs). A total of 12 healthy male (n = 6) and female (n = 6) Chinese volunteers were enrolled and completed the trial. After IV administration of single dose, the mean (SD) C_max value increased from 35.77 (6.98) to 117.12 (19.78) µg/mL, and the mean (SD) AUC_0-t value increased from 67.63 (10.30) to 230.50 (33.55) µg×h/mL in the range of 0.2-g to 0.8-g dose. The terminal half-life in plasma was ~ 2.0 hours. After IV administration of 9 doses of ibuprofen 400 mg every 6 hours, the mean (SD) C_max was 66.49 (8.49) µg/mL, the AUC_0-t was 135.65 (26.91) µg×h/mL, the t₁

Analysis of the data on pregnancy and lactation provided by patient information leaflets of anti-rheumatic drugs in Argentina.

PubMed

Sabando, Miguel Ormaza; Saavedra, Maira Arias; Sequeira, Gabriel; Kerzberg, Eduardo

2018-04-01

To analyse the level of consistency and updating of the information on pregnancy and lactation provided by patient information leaflets (PILs) of the antirheumatic drugs approved in Argentina. Inconsistencies between the 2016 EULAR Task Force recommendations on the use of anti-rheumatic drugs during pregnancy and lactation and the information provided by PILs of the same drugs approved in Argentina were analysed along with inconsistencies within the PILs of different registered trademarks of these drugs. Eighty-eight PILs of 32 drugs were analysed. Out of the 88 PILs, 50% presented information inconsistencies as to pregnancy. Medications comprised in this group were: hydroxychloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs (during the first two trimesters), celecoxib, some glucocorticoids, colchicine, and some anti-TNF drugs (etanercept, adalimumab and infliximab) during part of the pregnancy. As for lactation, 56% had information inconsistencies. Medications encompassed in this group were: hydroxychloroquine, chloroquine, sulfasalazine, azathioprine, tacrolimus, cyclosporine, NSAIDs, celecoxib, meprednisone, prednisone, colchicine, and anti-TNF drugs. Out of 17 drugs that had more than one registered trademark, information inconsistencies on pregnancy were found in the PILs of sulfasalazine, diclofenac, ibuprofen and methylprednisolone. Concerning lactation, inconsistencies were present in the PILs of hydroxychloroquine, sulfasalazine, diclofenac, ibuprofen, meprednisone, and colchicine. At least half of the PILs of anti-rheumatic drugs analysed in this study had information inconsistencies on pregnancy and lactation. This is a serious state of affairs because the consensual decision-making process between patient and professional may be compromised, which, in turn, may give rise to medical-legal issues.

A questionnaire based survey study for the evaluation of knowledge of Pakistani University teachers regarding their awareness about ibuprofen as an over the counter analgesic.

PubMed

Chen, Jianxian; Murtaza, Ghulam; Nadeem, Nida; Shao, Xiaokuai; Siddiqi, Bushra G; Shafique, Zainab; Ahmad, Saeed; Amjad, Seyyeda T; Haroon, Saima; Tanoli, Mamoona; Zhou, Mei

2014-01-01

In recent time, due to convenient availability of number of over the counter (OTC) drugs, patients are able to treat minor ailments by themselves. The self-medicated regimen has lead to certain health problems in all age groups irrespective of their professions. People are usually unaware about the safe use of NSAIDs (non-steroidal anti-inflammatory drugs) and currently there is no study carried out in COMSATS Institute of Information Technology (CIIT), Abbottabad, regarding the choice of faculty members for NSAIDs to relieve pain and their knowledge about its safety and use. A questionnaire based survey was carried out to collectdata about the choice of CIIT faculty for a specific NSAID and their cognition related to ibuprofen. Two hundred fifty faculty members (comprising of 53 pharmacy faculty members and 197 faculty members who belonged to other departments) of which 87 were females, took part in this study. Average age of participants was 34.86 +/- 9.02 years. Ibuprofen was the drug of choice NSAID among the participants. Four percent participants experienced pain almost every day. Analgesia was the well known indication for ibuprofen (31%) by both the groups and in general more educated and younger participants showed better apprehension related to indications. Sixty one percent participants comprising of non-pharmacy faculty were unaware of any undesirable effects and 79% (comprising of 72% pharmacists and 5% non-pharmacists) were affirmative that ibuprofen had no adverse effects. Fifteen percent participants of department other than pharmacy were not aware of any interactions of ibuprofen. 34% of participants (comprising of 32% non-pharmacists and 2% pharmacists) entrusted their physician for an analgesic. Regardless that many participants suffered from pain almost every day and their drug of choice would be ibuprofen, they had inadequate information related to the safety and use of ibuprofen.

The Prophylactic Effects of Zintoma and Ibuprofen on Post-endodontic Pain of Molars with Irreversible Pulpitis: A Randomized Clinical Trial

PubMed Central

Ramazani, Mohsen; Hamidi, Mahmoud Reza; Moghaddamnia, Ali Akbar; Ramazani, Nahid; Zarenejad, Nafiseh

2013-01-01

Introduction Post endodontic pain is often linked to the inflammatory process as well as additional central mechanisms. The purpose of the present double-blind randomized clinical trial study was to compare the prophylactic effects of a derivative of Zingiber Officinale, Zintoma, and Ibuprofen on post endodontic pain of molars with irreversible pulpitis. Materials and Methods The post endodontic pain of 72 enrolled patients suffering from irreversible pulpitis was assessed after prophylactic use of 400 mg Ibuprofen, 2 gr Zintoma and placebo. Using the Heft-Parker Visual Analogue Scale, the patients recorded their perceived pain before taking the medicament (baseline), immediately after and also at 4, 8, 12, 24, 48, and 72 h post one-visit endodontic treatment. The statistical analysis was done using Kruskal-Wallis, Mann-Whitney, and Freedman tests (P<0.05). Results At all times, there was significant difference between the Ibuprofen and Zintoma (P<0.05) and also between the Ibuprofen and placebo (P<0.05). However, there was no significant difference between Zintoma and the placebo in any of time intervals (P>0.05). No side effects were observed. Conclusion The obtained results of the trial revealed that prophylactic use of 2 gr Zintoma is not an effective pain relieving agent. PMID:23922575