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

Comparison of safety, efficacy and tolerability of dexibuprofen and ibuprofen in the treatment of osteoarthritis of the hip or knee.

PubMed

Zamani, Omid; Böttcher, Elke; Rieger, Jörg D; Mitterhuber, Johann; Hawel, Reinhold; Stallinger, Sylvia; Eller, Norbert

2014-06-01

In this observer-blinded, multicenter, non-inferiority study, 489 patients suffering from painful osteoarthritis of the hip or knee were included to investigate safety and tolerability of Dexibuprofen vs. Ibuprofen powder for oral suspension. Only patients who had everyday joint pain for the past 3 months and "moderate" to "severe" global pain intensity in the involved hip/knee of within the last 48 h were enrolled. The treatment period was up to 14 days with a control visit after 3 days. The test product was Dexibuprofen 400 mg powder for oral suspension (daily dose 800 mg) compared to Ibuprofen 400 mg powder for oral suspension (daily dose 1,600 mg). Gastrointestinal adverse drug reactions were reported in 8 patients (3.3 %) in the Dexibuprofen group and in 19 patients (7.8 %) in the Ibuprofen group. Statistically significant non-inferiority was shown for Dexibuprofen. Comparing both groups by a Chi square test showed a statistical significant lower proportion of related gastrointestinal events in the Dexibuprofen group. All analyses of secondary tolerability parameters showed the same result of a significantly better safety profile in this therapy setting for Dexibuprofen compared to Ibuprofen. The sum of pain intensity, pain relief and global assessments showed no significant difference between treatment groups. In summary, analyses revealed at least non-inferiority in terms of efficacy and a statistically significant better safety profile for the Dexibuprofen treatment.

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

Efficacy of Neurofeedback Versus Pharmacological Support in Subjects with ADHD.

PubMed

González-Castro, Paloma; Cueli, Marisol; Rodríguez, Celestino; García, Trinidad; Álvarez, Luis

2016-03-01

Behavioral training in neurofeedback has proven to be an essential complement to generalize the effects of pharmacological support in subjects who have attention deficit with hyperactivity disorder (ADHD). Therefore, this investigation attempts to analyze the efficacy of neurofeedback compared with pharmacological support and the combination of both. Participants were 131 students, classified into four groups: control (did not receive neurofeedback or pharmacological support), neurofeedback group, pharmacological support group, and combined group (neurofeedback + pharmacological support). Participants' executive control and cortical activation were assessed before and after treatment. Results indicate that the combined group obtained more benefits and that the neurofeedback group improved to a greater extent in executive control than the pharmacological support group. It is concluded that this kind of training may be an alternative to stimulate activation in subjects with ADHD.

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

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.

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 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

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.

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.

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).

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.

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.

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.

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

[Preliminary analysis on relationship between traditional efficacy of Chinese medicine and modern pharmacological action].

PubMed

Ren, Jun-Guo; Wang, Dong-Zhi; Lei, Lei; Kang, Li; Liu, Jian-Xun

2017-05-01

To find the relationship between traditional efficacy of Chinese medicine and modern pharmacological action by using data mining, and provide information and reference for further research and development for the pharmacology research of traditional Chinese medicine.The information of 547 kinds of traditional Chinese medicines, 335 kinds of Chinese medicine effects and 86 kinds of pharmacological actions were collected and processed in Clinical Guide to the Chinese Pharmacopoeia published in 2010; Access and Excel software were used to analyze the frequence and frequency of single effect, pharmacological action, and both. In addition, the relationship between efficacy and pharmacology was analyzed with the clearing heat and antibacterial effects as the example. The analysis results showed that 547 kinds of Chinese medicines involved 335 kinds of Chinese medicine effects and 86 kinds of pharmacological actions. Among them, the most frequent Chinese medicine effect was"clearing heat", whose frequence was 130 and the frequency was 0.24; the most frequent pharmacological action was "anti-inflammatory action" whose frequence was 191 and the frequency was 0.35. The most common efficacy-pharmacological action group was "clearing heat" and "anti-bacterial action", whose frequence was 75 and the frequency was 0.26. The couple of "purgation" and "cathartic effect" had the largest frequency of 0.30, but they just appeared together for 3 times. There were 52 kinds of pharmacological actions that occurred together with clearing heat, of which, the top 10 were anti-bacterial action, anti-inflammatory action, antineoplastic action, anti-hepatic injury action, immunoregulation action, antipyretic action, antiviralaction, hypoglycemic action, antioxidant action and analgesic action. There were 161 kinds of Chinese medicine effects that occurred together with anti-bacterial action, of which, the top 10 were clearing heat, detoxification, detumescence, analgesia, resolving dampness

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.

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.

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.

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.

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.

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.

Is psychological treatment efficacious for attention deficit hyperactivity disorder (ADHD)? Review of non-pharmacological treatments in children and adolescents with ADHD.

PubMed

Serrano-Troncoso, Eduardo; Guidi, Monica; Alda-Díez, José Ángel

2013-01-01

Attention deficit hyperactivity disorder (ADHD) is the most prevalent psychiatric disorder in children and adolescents, and has a great impact on the psychological development of affected patients. Even though its efficacy is proven, the use of medication for ADHD has several limitations, and non-pharmacological interventions are considered a necessary component of treatment. This work is a review of evidence-based non-pharmacological treatments with demonstrated efficacy for ADHD in children and adolescents, analyzed by age groups. Non-pharmacological treatments that have shown scientific evidence of efficacy are psychological and psychoeducational interventions. Psychological interventions include behavioral therapy, parent training (PT) and social skills training. Psychoeducational interventions include a set of practices to improve learning and are carried out in the school setting. Scientific evidence of efficacy in preschool children is limited to PT, while different psychological and psychoeducational interventions have been shown to be beneficial in school-age children. The available evidence for non-pharmacological treatment in adolescence is so far insufficient. Though more randomized controlled trials are necessary for non-pharmacological interventions to become established practices, there are clear indications of their efficacy. For more severe cases of ADHD, a combination of non-pharmacological and pharmacological treatment is recommended.

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

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.

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.

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

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.

Equivalent intraperitoneal doses of ibuprofen supplemented in drinking water or in diet: a behavioral and biochemical assay using antinociceptive and thromboxane inhibitory dose–response curves in mice

PubMed Central

El Gayar, Nesreen H.; Georgy, Sonia S.

2016-01-01

Background. Ibuprofen is used chronically in different animal models of inflammation by administration in drinking water or in diet due to its short half-life. Though this practice has been used for years, ibuprofen doses were never assayed against parenteral dose–response curves. This study aims at identifying the equivalent intraperitoneal (i.p.) doses of ibuprofen, when it is administered in drinking water or in diet. Methods. Bioassays were performed using formalin test and incisional pain model for antinociceptive efficacy and serum TXB2 for eicosanoid inhibitory activity. The dose–response curve of i.p. administered ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg body weight (b.w.). The dose–response curves were constructed of phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents), the area under the ‘change in mechanical threshold’-time curve in the incisional pain model and serum TXB2 levels. The assayed ibuprofen concentrations administered in drinking water were 0.2, 0.35, 0.6 mg/ml and those administered in diet were 82, 263, 375 mg/kg diet. Results. The 3 concentrations applied in drinking water lay between 73.6 and 85.5 mg/kg b.w., i.p., in case of the formalin test; between 58.9 and 77.8 mg/kg b.w., i.p., in case of the incisional pain model; and between 71.8 and 125.8 mg/kg b.w., i.p., in case of serum TXB2 levels. The 3 concentrations administered in diet lay between 67.6 and 83.8 mg/kg b.w., i.p., in case of the formalin test; between 52.7 and 68.6 mg/kg b.w., i.p., in case of the incisional pain model; and between 63.6 and 92.5 mg/kg b.w., i.p., in case of serum TXB2 levels. Discussion. The increment in pharmacological effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those of i.p. administered ibuprofen. It is therefore difficult to assume the equivalent parenteral daily doses based on mathematical calculations. PMID:27547547

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

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 ...

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.

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.

[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.

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.

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.

Efficacy of Codeine When Added to Paracetamol (Acetaminophen) and Ibuprofen for Relief of Postoperative Pain After Surgical Removal of Impacted Third Molars: A Double-Blinded Randomized Control Trial.

PubMed

Best, Adrian D; De Silva, R K; Thomson, W M; Tong, Darryl C; Cameron, Claire M; De Silva, Harsha L

2017-10-01

The use of opioids in combination with nonopioids is common practice for acute pain management after third molar surgery. One such combination is paracetamol, ibuprofen, and codeine. The authors assessed the efficacy of codeine when added to a regimen of paracetamol and ibuprofen for pain relief after third molar surgery. This study was a randomized, double-blinded, placebo-controlled trial conducted in patients undergoing the surgical removal of at least 1 impacted mandibular third molar requiring bone removal. Participants were randomly allocated to a control group (paracetamol 1,000 mg and ibuprofen 400 mg) or an intervention group (paracetamol 1,000 mg, ibuprofen 400 mg, and codeine 60 mg). All participants were treated under intravenous sedation and using identical surgical conditions and technique. Postoperative pain was assessed using the visual analog scale (VAS) every 3 hours (while awake) for the first 48 hours after surgery. Pain was globally assessed using a questionnaire on day 3 after surgery. There were 131 participants (36% men; control group, n = 67; intervention group, n = 64). Baseline characteristics were similar for the 2 groups. Data were analyzed using a modified intention-to-treat analysis and, for this, a linear mixed model was used. The model showed that the baseline VAS score was associated with subsequent VAS scores and that, with each 3-hour period, the VAS score increased by an average of 0.08. The treatment effect was not statistically meaningful, indicating there was no difference in recorded pain levels between the 2 groups during the first 48 hours after mandibular third molar surgery. Similarly, the 2 groups did not differ in their global ratings of postoperative pain. Codeine 60 mg added to a regimen of paracetamol 1,000 mg and ibuprofen 400 mg does not improve analgesia after third molar surgery. Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights

Regioselective reaction: synthesis and pharmacological study of Mannich bases containing ibuprofen moiety.

PubMed

Sujith, K V; Rao, Jyothi N; Shetty, Prashanth; Kalluraya, Balakrishna

2009-09-01

A series of 4-[(4-aryl)methylidene]amino-2-(substituted-4-ylmethyl)-5-{1-[4-(2-methylpropyl)phenyl]ethyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione (6) were synthesized from an arylpropionic acid namely, ibuprofen by a three-component Mannich reaction. Aminomethylation of 4-[(4-aryl)methylidene]amino-5-{1-[4-(2-methylpropyl)phenyl] ethyl}-4H-1,2,4-triazole-3-thiol (5) with formaldehyde and a secondary amine furnished this novel series of Mannich bases (6). Both Schiff bases (5) and Mannich bases (6) were well characterized on the basis of IR, NMR, mass spectral data and elemental analysis. They were screened for their anti-inflammatory, analgesic, antibacterial and antifungal activities. Some of the Mannich bases (6) carrying morpholino and N-methylpiperazino residues were found to be promising anti-inflammatory and analgesic agents.

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.

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

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.

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

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 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.

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.

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.

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

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

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.

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

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

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

Thai Massage, and Thai Herbal Compress versus Oral Ibuprofen in Symptomatic Treatment of Osteoarthritis of the Knee: A Randomized Controlled Trial

PubMed Central

2014-01-01

The aim of this study was to verify the clinical responses to Thai massage (TM) and Thai herbal compression (THC) for treating osteoarthritis (OA) of the knee in comparison to oral ibuprofen. This study was a randomized, evaluator-blind, controlled trial. Sixty patients with OA of the knee were randomly assigned to receive either a one-hour session of TM or THC (three times weekly) or oral ibuprofen (three times daily). The duration of treatment was three weeks. The clinical assessments included visual analog scale assessing pain and stiffness, Lequesne's functional index, time for climbing up ten steps, and physician's and patient's overall opinions on improvement. In a within-group comparison, each treatment modality caused a significant improvement of all variables determined for outcome assessments. In an among group comparison, all modalities provided nearly comparable clinical efficacy after a three-week symptomatic treatment of OA of the knee, in which a trend toward greatest improvement was likely to be found in THC group. In conclusion, TM and THC generally provided comparable clinical efficacy to oral ibuprofen after three weeks of treatment and could be considered as complementary and alternative treatments for OA of the knee. PMID:25254207

The novel agent phospho-glycerol-ibuprofen-amide (MDC-330) inhibits glioblastoma growth in mice: an effect mediated by cyclin D1

PubMed Central

Bartels, Lauren E.; Mattheolabakis, George; Vaeth, Brandon M.; LaComb, Joseph F.; Wang, Ruixue; Zhi, Jizu; Komninou, Despina; Rigas, Basil; Mackenzie, Gerardo G.

2016-01-01

Given that glioblastoma multiforme (GBM) is associated with poor prognosis, new agents are urgently needed. We developed phospho-glycerol-ibuprofen-amide (PGIA), a novel ibuprofen derivative, and evaluated its safety and efficacy in preclinical models of GBM, and its mechanism of action using human GBM cells and animal tumor models. Furthermore, we explored whether formulating PGIA in polymeric nanoparticles could enhance its levels in the brain. PGIA was 3.7- to 5.1-fold more potent than ibuprofen in suppressing the growth of human GBM cell lines. PGIA 0.75× IC50 inhibited cell proliferation by 91 and 87% in human LN-229 and U87-MG GBM cells, respectively, and induced strong G1/S arrest. In vivo, compared with control, PGIA reduced U118-MG and U87-MG xenograft growth by 77 and 56%, respectively (P < 0.05), and was >2-fold more efficacious than ibuprofen. Normal human astrocytes were resistant to PGIA, indicating selectivity. Mechanistically, PGIA reduced cyclin D1 levels in a time- and concentration-dependent manner in GBM cells and in xenografts. PGIA induced cyclin D1 degradation via the proteasome pathway and induced dephosphorylation of GSK3β, which was required for cyclin D1 turnover. Furthermore, cyclin D1 overexpression rescued GBM cells from the cell growth inhibition by PGIA. Moreover, the formulation of PGIA in poly-(l)-lactic acid poly(ethylene glycol) polymeric nanoparticles improved its pharmacokinetics in mice, delivering PGIA to the brain. PGIA displays strong efficacy against GBM, crosses the blood-brain barrier when properly formulated, reaching the target tissue, and establishes cyclin D1 as an important molecular target. Thus, PGIA merits further evaluation as a potential therapeutic option for GBM. PMID:26905586

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.

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.

Comparative evaluation of effect of preoperative oral medication of ibuprofen and ketorolac on anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients with irreversible pulpitis: a prospective, double-blind, randomized clinical trial.

PubMed

Aggarwal, Vivek; Singla, Mamta; Kabi, Debipada

2010-03-01

Anesthetic efficacy of inferior alveolar nerve block decreases in patients with irreversible pulpitis. It was hypothesized that premedication with nonsteroidal anti-inflammatory drugs might improve the success rates in patients with inflamed pulps. Sixty-nine adult volunteers who were actively experiencing pain participated in this prospective, randomized, double-blind study. The patients were divided into 3 groups on a random basis and were randomly given 1 of the 3 drugs including ibuprofen, ketorolac, and placebo 1 hour before anesthesia. All patients received standard inferior alveolar nerve block of 2% lidocaine with 1:200,000 epinephrine. Endodontic access preparation was initiated after 15 minutes of initial inferior alveolar nerve block. Pain during treatment was recorded by using a Heft Parker visual analog scale. Success was recorded as none or mild pain. Statistical analysis with nonparametric chi2 tests showed that placebo gave 29% success rate. Premedication with ibuprofen gave 27%, and premedication with ketorolac gave 39% success rate. There was no significant difference between the 3 groups. Preoperative administration of ibuprofen or ketorolac has no significant effect on success rate of inferior alveolar nerve block in patients with irreversible pulpitis. Copyright (c) 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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.

A 12-week, double-blind, multicenter study comparing diflunisal twice daily and ibuprofen four times daily in the treatment of rheumatoid arthritis.

PubMed

Bennett, R M

1986-01-01

Diflunisal, a nonacetylated salicylate preparation with a prolonged duration of action, was compared with ibuprofen for the treatment of rheumatoid arthritis in a multicenter trial comprising 210 patients. Diflunisal was administered twice a day (500 to 750 mg/day) and ibuprofen was administered four times a day (1,600 to 2,400 mg/day). To maintain double-blind conditions, all patients ostensibly followed the same regimen, ingesting their assigned drug and a matching placebo of their nonassigned drug. Disease activity assessments and laboratory tests were done periodically throughout the 12 weeks of the study, and results were compared with pretreatment findings. Efficacy evaluations in 187 patients showed that both treatments were similarly efficacious. Safety and tolerability also were similar in the two groups. Diflunisal, however, offers a more acceptable BID treatment schedule.

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.

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

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

A comparison of the efficacy of newly developed reversible inhibitors of acetylcholinesterase with commonly used pyridostigmine as pharmacological pre-treatment of soman-poisoned mice.

PubMed

Kassa, Jiri; Musilek, Kamil; Koomlova, Marketa; Bajgar, Jiri

2012-04-01

The ability of three newly developed reversible inhibitors of acetylcholinesterase (AChE) (K298, K344 and K474) and currently available carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was compared. Neither pyridostigmine nor new reversible inhibitors of AChE were able to increase the LD(50) value of soman. Thus, the pharmacological pre-treatment with pyridostigmine or newly synthesized inhibitors of AChE was not able to protect mice against soman-induced lethal acute toxicity. The pharmacological pre-treatment with pyridostigmine alone or with K474 was able to slightly increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice, but the increase in the efficacy of antidotal treatment was not significant. The other newly developed reversible inhibitors of AChF (K298, K344) were completely ineffective. These findings demonstrate that pharmacological pre-treatment of soman-poisoned mice with tested reversible inhibitors of AChF is not promising. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

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.

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...

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

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.

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.

Pharmacological interaction between oxcarbazepine and two COX inhibitors in a rat model of inflammatory hyperalgesia.

PubMed

Stepanović-Petrović, Radica M; Tomić, Maja A; Vučković, Sonja M; Poznanović, Goran; Ugrešić, Nenad D; Prostran, Milica Š; Bošković, Bogdan

2011-01-01

Oxcarbazepine, ibuprofen and etodolac have efficacy in inflammatory pain. The combination of different drugs activates both central and peripheral pain inhibitory pathways to induce additive or synergistic antinociception, and this interaction may allow lower doses of each drug combined and improve the safety profile, with lower side-effects. This study aimed to examine the effects of oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations, in a rat model of inflammatory hyperalgesia, and determine the type of interaction between drugs. Rats were intraplantarly injected with carrageenan (0.1 ml, 1%) and the hyperalgesia was assessed by modified paw pressure test. The anti-hyperalgesic effects of oxcarbazepine, ibuprofen and etodolac and oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations were examined. Drugs were co-administered in a fixed-dose fractions of the ED₅₀ and the type of interaction was determined by isobolographic analysis. Oxcarbazepine (40-160 mg/kg; p.o.), ibuprofen (10-120 mg/kg; p.o.) and etodolac (5-20 mg/kg; p.o.) produced a significant, dose-dependent anti-hyperalgesia in carrageenan-injected rats. ED₅₀ values (mean±SEM) for oxcarbazepine, ibuprofen and etodolac were 88.17±3.65, 47.07±10.27 and 13.05±1.42 mg/kg, respectively. Oxcarbazepine-ibuprofen and oxcarbazepine-etodolac combinations induced significant and dose-dependent anti-hyperalgesia. Isobolographic analysis revealed that oxcarbazepine exerts a synergistic interaction with ibuprofen, with almost 4-fold reduction of doses of both drugs in combination. In contrast, there was an additive interaction with etodolac. Synergistic interaction of oxcarbazepine with ibuprofen and its additive interaction with etodolac provide new information about the combination pain treatment and could be explored further in patients with inflammatory pain. Adverse effect analysis of the combinations is necessary to verify possible clinical use of the mixtures. Copyright �

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 ...

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

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

Safety and efficacy of pharmacologic thromboprophylaxis following blunt head injury: a systematic review.

PubMed

Reeves, Fairleigh; Batty, Lachlan; Pitt, Veronica; Chau, Marisa; Pattuwage, Loyal; Gruen, Russell L

2013-10-01

Patients with blunt head injury are at high risk of venous thromboembolism. However, pharmacologic thromboprophylaxis (PTP) may cause progression of intracranial hemorrhage, and clinicians must often weigh up the risks and benefits. This review aimed to determine whether adding PTP to mechanical prophylaxis confers net benefit or harm and the optimal timing, dose, and agent for PTP in patients with blunt head injury. We searched MEDLINE, EMBASE, The Cochrane Library Central Register of Controlled Trials (CENTRAL), and www.clinicaltrials.gov on April 24, 2013, to identify controlled studies and ongoing trials that assessed the efficacy or safety of thromboprophylaxis interventions in the early management of head-injured patients. Studies were classified based on types of interventions and comparisons, and the quality of included studies was assessed using Cochrane risk-of-bias tool and the Newcastle-Ottawa Quality Assessment Scale. We intended to undertake a meta-analysis if studies were sufficiently similar. Sixteen studies met the inclusion criteria, including four randomized controlled trials. At least two randomized controlled trials were at high risk of bias owing to inadequate randomization and concealment of allocation, and observational studies were potentially confounded by substantial differences between comparison groups. Heterogeneity of included studies precluded meta-analysis. Results were mixed, with some studies supporting and others refuting addition of PTP to mechanical interventions. Little evidence was available about dose or choice of agent. The safety and efficacy of early PTP in patients without early progression of hemorrhage is unclear. There is currently insufficient evidence to guide thromboprophylaxis in patients with blunt head injury. Standardized definitions and outcome measurements would facilitate comparison of outcomes across future studies. Studies in mixed populations should report head-injured specific subgroup data. Future

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.

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.

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

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.

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.

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.

Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis.

PubMed

Nissen, Steven E; Yeomans, Neville D; Solomon, Daniel H; Lüscher, Thomas F; Libby, Peter; Husni, M Elaine; Graham, David Y; Borer, Jeffrey S; Wisniewski, Lisa M; Wolski, Katherine E; Wang, Qiuqing; Menon, Venu; Ruschitzka, Frank; Gaffney, Michael; Beckerman, Bruce; Berger, Manuela F; Bao, Weihang; Lincoff, A Michael

2016-12-29

The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain. Patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. Noninferiority required a hazard ratio of 1.12 or lower, as well as an upper 97.5% confidence limit of 1.33 or lower in the intention-to-treat population and of 1.40 or lower in the on-treatment population. Gastrointestinal and renal outcomes were also adjudicated. A total of 24,081 patients were randomly assigned to the celecoxib group (mean [±SD] daily dose, 209±37 mg), the naproxen group (852±103 mg), or the ibuprofen group (2045±246 mg) for a mean treatment duration of 20.3±16.0 months and a mean follow-up period of 34.1±13.4 months. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up. In the intention-to-treat analyses, a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%) (hazard ratio for celecoxib vs. naproxen, 0.93; 95% confidence interval [CI], 0.76 to 1.13; hazard ratio for celecoxib vs. ibuprofen, 0.85; 95% CI, 0.70 to 1.04; P<0.001 for noninferiority in both comparisons). In the on-treatment analysis, a primary outcome event occurred in 134 patients in the celecoxib group (1.7%), 144 patients in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) (hazard ratio for celecoxib vs. naproxen, 0.90; 95% CI, 0.71 to 1.15; hazard ratio for celecoxib vs. ibuprofen, 0.81; 95% CI, 0.65 to 1.02; P<0.001 for noninferiority in

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.

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.

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.

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

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.

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.

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

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.

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.

Comparison of the efficacy and safety of nonprescription doses of naproxen and naproxen sodium with ibuprofen, acetaminophen, and placebo in the treatment of primary dysmenorrhea: a pooled analysis of five studies.

PubMed

Milsom, Ian; Minic, Milos; Dawood, M Yusoff; Akin, Mark D; Spann, June; Niland, Nona F; Squire, R Anne

2002-09-01

Dysmenorrhea is the most common menstrual complaint in young women, with a prevalence as high as 90%. It is responsible for substantial repeated short-term absenteeism from school and work in young women. Effective treatments are available, including nonsteroidal anti-inflammatory drugs (NSAIDs). In many countries, a variety of NSAIDs have become available as over-the-counter (OTC) drugs. The goal of this study was to compare the efficacy and safety of OTC doses of naproxen (400 mg) and naproxen/naproxen sodium (200/220 mg) with acetaminophen (1000 mg), ibuprofen (200 mg), and placebo in the treatment of primary dysmenorrhea. A pooled analysis of 5 trials was performed. Efficacy was assessed by pain relief, relief of other dysmenorrheic symptoms, time to backup medication or remedication, and treatment preference. Tolerability was assessed by recording adverse events (AEs). A total of 443 women were enrolled in the combined studies. Naproxen 400 mg provided greater pain relief than acetaminophen and placebo within 30 minutes of administration (P < 0.01 and P < 0.05, respectively). Furthermore, naproxen 400 mg and 200 mg provided greater pain relief than both acetaminophen (P < 0.01 and P < 0.05, respectively) and ibuprofen (P < 0.001 and P < 0.01, respectively) at 6 hours after administration. Both doses of naproxen had higher scores than placebo for symptom relief and drug preference (all P < 0.001). The AEs and their frequency were similar among the treatment groups. No serious AEs were reported. When administered at OTC doses, naproxen was effective in the relief of pain and other symptoms of primary dysmenorrhea and had a good safety profile in the population studied.

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

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.

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.

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

The importance of stress, self-efficacy, and self-medication for pharmacological neuroenhancement among employees and students.

PubMed

Maier, Larissa J; Haug, Severin; Schaub, Michael P

2015-11-01

This study examined the relationship between stress, self-efficacy, self-medication, and pharmacological neuroenhancement (PNE) in the Swiss general population. Using the largest Swiss Internet panel, a sample of 10,171 employees and students (unweighted N=10,084) aged 15-74 years was recruited and asked to complete a self-administered online survey. The data were weighted for age, sex, and language region to provide results that were representative of the Swiss population. Multinomial logistic regression models were conducted to identify predictors of pharmacological cognitive enhancement (PCE) and pharmacological mood enhancement (PME) over the past year. Two self-medication models and an overall model were determined. Current medical treatment for a mental disorder was the best predictor of both PCE and PME use as serious self-medication. The overall model revealed that cannabis use, frequent stress, and long-term stress were predictors of both PCE and PME, whereas negative stressors and time pressure at work did not remain in the final model. Furthermore, past-year PCE with and without PME was associated with being male, being a student, and using illegal drugs other than cannabis, whereas being female and having low self-efficacy predicted past-year PME only. Consideration of the predictor variables identified in this study may help to identify the potential PCE and PME users for whom measures to prevent drug abuse and manage stress are most appropriate. More specifically, the use of PCE and PME as self-medication to enhance performance at work or while studying needs further consideration in the neuroenhancement debate. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

Paracetamol versus ibuprofen for the treatment of patent ductus arteriosus in preterm neonates: a meta-analysis of randomized controlled trials.

PubMed

Huang, Xintao; Wang, Fang; Wang, Kai

2018-08-01

Paracetamol has been suggested as an effective treatment for patent ductus arteriosus (PDA). However, the comparative efficacy and safety between paracetamol and ibuprofen were not determined. A meta-analysis of randomized controlled trials (RCTs) was performed. Relevant studies were identified via database searching. A fixed or random effect model was applied depending on the extent of heterogeneity. Five RCTs with 677 neonates were included. The efficacies for the primary (risk ratio [RR]: 1.03, p = .56) and overall PDA closure were comparable between the two medications (RR: 1.02, p = .62). Neonates of the two groups were comparable for the incidence of PDA complications, including necrotizing enterocolitis (RR: 0.86, p = .70), intraventricular hemorrhage (RR: 0.84, p = .55), bronchopulmonary dysplasia (RR: 0.69, p = .16), and retinopathy of prematurity (RR: 0.58, p = .15), and the risks of sepsis (RR = 0.88, p = .48) and death (RR: 1.45, p = .45) within hospitalization. However, treatment with paracetamol was associated with a trend of reduced risk of renal failure (RR: 0.20, p = .07), and a significantly reduced risk of gastrointestinal bleeding (RR: 0.28, p = .009). Paracetamol may confer comparable treatment efficacy for the closure of PDA as ibuprofen, although paracetamol is associated with lower risk of adverse events.

Intravenous non-opioid analgesia for peri- and postoperative pain management: a scientific review of intravenous acetaminophen and ibuprofen

PubMed Central

Koh, Wonuk; Nguyen, Kimngan Pham

2015-01-01

Pain is a predictable consequence following operations, but the management of postoperative pain is another challenge for anesthesiologists and inappropriately controlled pain may lead to unwanted outcomes in the postoperative period. Opioids are indeed still at the mainstream of postoperative pain control, but solely using only opioids for postoperative pain management may be connected with risks of complications and adverse effects. As a consequence, the concept of multimodal analgesia has been proposed and is recommended whenever possible. Acetaminophen is one of the most commonly used analgesic and antipyretic drug for its good tolerance and high safety profiles. The introduction of intravenous form of acetaminophen has led to a wider flexibility of its use during peri- and postoperative periods, allowing the early initiation of multimodal analgesia. Many studies have revealed the efficacy, safety and opioid sparing effects of intravenous acetaminophen. Intravenous ibuprofen has also shown to be well tolerated and demonstrated to have significant opioid sparing effects during the postoperative period. However, the number of randomized controlled trials confirming the efficacy and safety is small and should be used in caution in certain group of patients. Intravenous acetaminophen and ibuprofen are important options for multimodal postoperative analgesia, improving pain and patient satisfaction. PMID:25664148

Intravenous non-opioid analgesia for peri- and postoperative pain management: a scientific review of intravenous acetaminophen and ibuprofen.

PubMed

Koh, Wonuk; Nguyen, Kimngan Pham; Jahr, Jonathan S

2015-02-01

Pain is a predictable consequence following operations, but the management of postoperative pain is another challenge for anesthesiologists and inappropriately controlled pain may lead to unwanted outcomes in the postoperative period. Opioids are indeed still at the mainstream of postoperative pain control, but solely using only opioids for postoperative pain management may be connected with risks of complications and adverse effects. As a consequence, the concept of multimodal analgesia has been proposed and is recommended whenever possible. Acetaminophen is one of the most commonly used analgesic and antipyretic drug for its good tolerance and high safety profiles. The introduction of intravenous form of acetaminophen has led to a wider flexibility of its use during peri- and postoperative periods, allowing the early initiation of multimodal analgesia. Many studies have revealed the efficacy, safety and opioid sparing effects of intravenous acetaminophen. Intravenous ibuprofen has also shown to be well tolerated and demonstrated to have significant opioid sparing effects during the postoperative period. However, the number of randomized controlled trials confirming the efficacy and safety is small and should be used in caution in certain group of patients. Intravenous acetaminophen and ibuprofen are important options for multimodal postoperative analgesia, improving pain and patient satisfaction.

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.

Comparison of Effect of Oral Premedication with Ibuprofen or Dexamethasone on Anesthetic Efficacy of Inferior Alveolar Nerve Block in Patients with Irreversible Pulpitis: A Prospective, Randomized, Controlled, Double-blind Study.

PubMed

Bidar, Maryam; Mortazavi, Soheil; Forghani, Maryam; Akhlaghi, Saeed

2017-01-01

The purpose of this prospective, randomized, double-blind, placebo-controlled study was to determine the effect of preoperative oral administration of ibuprofen or dexamethasone on the success rate of inferior alveolar nerve block (IANB) in patients with symptomatic irreversible pulpitis. Seventy-eight patients with irreversible pulpitis were randomly divided into 3 groups (26 per group) and given one of the following at 1 hr prior to performing local anesthesia: a placebo; 400 mg ibuprofen; or 4 mg dexamethasone. Each patient recorded their pain level on a visual analog scale before taking the medication or placebo, at 15 min after completion of IANB, and during treatment if pain occurred. The success of the anesthesia was defined as no or mild pain at any stage during the endodontic procedure. The success rate of the IANB was 38.5, 73.1, and 80.8% with the placebo, ibuprofen, and dexamethasone, respectively. Both ibuprofen and dexamethasone were significantly more effective than the placebo. No significant difference was observed, however, between the two experimental medications in terms of effectiveness. The results of the present study suggest that premedication with ibuprofen or dexamethasone increases the success rate of an IANB in patients with symptomatic irreversible pulpitis in the mandibular molars.

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.

The pharmacology of palmitoylethanolamide and first data on the therapeutic efficacy of some of its new formulations.

PubMed

Petrosino, Stefania; Di Marzo, Vincenzo

2017-06-01

Palmitoylethanolamide (PEA) has emerged as a potential nutraceutical, because this compound is naturally produced in many plant and animal food sources, as well as in cells and tissues of mammals, and endowed with important neuroprotective, anti-inflammatory and analgesic actions. Several efforts have been made to identify the molecular mechanism of action of PEA and explain its multiple effects both in the central and the peripheral nervous system. Here, we provide an overview of the pharmacology, efficacy and safety of PEA in neurodegenerative disorders, pain perception and inflammatory diseases. The current knowledge of new formulations of PEA with smaller particle size (i.e. micronized and ultra-micronized) when given alone or in combination with antioxidant flavonoids (i.e. luteolin) and stilbenes (i.e. polydatin) is also reviewed. This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc. © 2016 The British Pharmacological Society.

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.

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.

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.

Review of pharmacological therapy for tinnitus.

PubMed

Patterson, Matthew B; Balough, Ben J

2006-01-01

This article provides a review of studies investigating the pharmacological treatment of tinnitus. Tinnitus continues to be a significant and costly health problem without a uniformly accepted treatment. A wide variety of studies exploring prescription, supplement, and vitamin therapies are assessed for efficacy of treatment and for establishing consistencies in symptom definition, assessment, and outcome measures. This review reveals no compelling evidence suggesting the efficacy of any pharmacological agent in the treatment of tinnitus. Analysis of prior investigations provides insight to appropriate methods for future work, which are outlined.

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

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.

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.

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

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.

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.

Effect of Aspirin Coadministration on the Safety of Celecoxib, Naproxen, or Ibuprofen.

PubMed

Reed, Grant W; Abdallah, Mouin S; Shao, Mingyuan; Wolski, Kathy; Wisniewski, Lisa; Yeomans, Neville; Lüscher, Thomas F; Borer, Jeffrey S; Graham, David Y; Husni, M Elaine; Solomon, Daniel H; Libby, Peter; Menon, Venu; Lincoff, A Michael; Nissen, Steven E

2018-04-24

The safety of nonsteroidal anti-inflammatory drug (NSAID) and aspirin coadministration is uncertain. The aim of this study was to compare the safety of combining NSAIDs with low-dose aspirin. This analysis of the PRECISION (Prospective Randomized Evaluation of Celecoxib Integrated Safety Versus Ibuprofen or Naproxen) trial included 23,953 patients with osteoarthritis or rheumatoid arthritis at increased cardiovascular risk randomized to celecoxib, ibuprofen, or naproxen. The on-treatment population was used for this study. Outcomes included composite major adverse cardiovascular events, noncardiovascular death, gastrointestinal or renal events, and components of the composite. Cox proportional hazards models compared outcomes among NSAIDs stratified by aspirin use following propensity score adjustment. Kaplan-Meier analysis was used to compare the cumulative probability of events. When taken without aspirin, naproxen or ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.22 to 1.90, p <0.001; and HR: 1.81; 95% CI: 1.46 to 2.26; p <0.001, respectively). Compared with celecoxib, ibuprofen had more major adverse cardiovascular events (p < 0.05), and both ibuprofen and naproxen had more gastrointestinal (p < 0.001) and renal (p < 0.05) events. Taken with aspirin, ibuprofen had greater risk for the primary composite endpoint compared with celecoxib (HR: 1.27; 95% CI: 1.06 to 1.51; p < 0.01); this was not significantly higher with naproxen (HR: 1.18; 95% CI: 0.98 to 1.41; p = 0.08). Among patients on aspirin, major adverse cardiovascular events were similar among NSAIDs, and compared with celecoxib, ibuprofen had more gastrointestinal and renal events (p < 0.05), while naproxen had more gastrointestinal events (p < 0.05), without a difference in renal events. Similar results were seen on adjusted Kaplan-Meier analysis. Celecoxib has a more favorable overall safety

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.

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

Synthesis and antinociceptive evaluation of bioisosteres and hybrids of naproxen, ibuprofen and paracetamol.

PubMed

González-Trujano, María Eva; Uribe-Figueroa, Gerardo; Hidalgo-Figueroa, Sergio; Martínez, Ana Laura; Déciga-Campos, Myrna; Navarrete-Vazquez, Gabriel

2018-05-01

The aim of this work was to design, synthesize and characterize the potential anti-nociceptive and anti-inflammatory activities of a new series of bioisosteres and hybrids from known non-steroidal anti-inflammatory drugs (NSAIDs). The compounds 4-(acetylamino)phenyl (2S)-2-(6-methoxy-2-naphthyl)propanoate (GUF-1) and 4-(acetylamino)phenyl 2-(R,S)-(4-isobutylphenyl)propanoate (GUF-2) were synthesized as hybrids (also known as heterodimers); whereas those named 2-(R,S)-(4-isobutylphenyl)-N-1H-tetrazol-5-ylpropanamide (GUF-3), (2S)-2-(6-methoxy-2-naphthyl)-N-1H-tetrazol-5-ylpropanamide (GUF-4), [2-(R,S)-N-hydroxy-2-[4-(2-methylpropyl)phenyl]propanamide] (GUF-5), and (2S)-N-hydroxy-2-(6-methoxy-2-naphthyl)propanamide (GUF-6) were synthesized as bioisosteres of the NSAIDs paracetamol, ibuprofen, and naproxen, respectively. All these compounds were characterized by spectroscopic and spectrometric analysis. Antinociceptive activity of GUF-1 to GUF-6 was evaluated using the formalin test in rats. Pharmacological responses of GUF-1, GUF-2 (hybrids), and GUF-5 (bioisostere) demonstrated significant antinociceptive effects; thus these compounds were assayed in an inflammation test like carrageenan-induced paw oedema in rats. Complete molecular docking of cyclooxygenase and the GUF-1 and GUF-2 hybrids showed high docking scores, compared to the reference drugs. Our data demonstrate that compounds GUF-1, GUF-2, and GUF-5 possesses antinociceptive and antiinflammatory activities resembling and improving those known for the traditional NSAIDs, paracetamol, naproxen and ibuprofen. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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.

Efficacy and Pharmacological Mechanism of Pronase-Enhanced Low-Dose Antibiotics for Helicobacter pylori Eradication

PubMed Central

Liu, Kai Y.; Du, Fang C.; Fu, Qiang; Zhang, Wei J.; Sun, Hong W.; Zhang, Yi; Gan, Le L.; Yue, Zhi Y.

2014-01-01

This study examined the efficacy and pharmacological mechanism of pronase-assisted low-dose antibiotics for eradication of Helicobacter pylori. Mongolian gerbils infected with H. pylori received 7-day treatment (omeprazole, different concentrations of pronase, amoxicillin, and clarithromycin), and the efficacy was assessed using the eradication rate and the colonization of H. pylori. In Mongolian gerbils orally administered pronase, the thickness of the gastric mucous layer (GML) was examined using immunohistochemical and alcian blue staining, and the concentrations of amoxicillin in gastric tissue and serum were detected using high-performance liquid chromatography (HPLC). The eradication rates were 80.0% (12/15) in the high-pronase quadruple group (HPQG) and 86.7% (13/15) in the high-antibiotic group (HAG) (P = 1.000). The antibiotic dose in the HPQG was only 1/20 that in the HAG. Thirty minutes after oral treatment with pronase, the sticky protein of the GML was hydrolyzed, and the GML became thinner. Higher amoxicillin concentrations in both the gastric tissue and serum were observed in the pronase group than in the Am10 group. The concentration of amoxicillin in the Am10-plus-Pr108 group in gastric tissue was 3.8 times higher than in the Am10 group in 5 min. Together, these data suggest that pronase significantly reduced the dose of antibiotics used in H. pylori eradication. The pharmacological mechanism is likely pronase removal of the mucus layer, promoting chemical factor (i.e., gastric acid and pepsinogen) distribution and increasing the antibiotic concentrations in the deep GML, which acted on H. pylori collectively. Thus, pronase may enhance the level of antibiotics for eradication of H. pylori in the clinic. PMID:24687504

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

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

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.

Pharmacology of the Phosphate Binder, Lanthanum Carbonate

PubMed Central

Damment, Stephen JP

2011-01-01

Studies were conducted to compare the phosphate-binding efficacy of lanthanum carbonate directly with other clinically used phosphate binders and to evaluate any potential adverse pharmacology. To examine the phosphate-binding efficacy, rats with normal renal function and chronic renal failure received lanthanum carbonate, aluminum hydroxide, calcium carbonate, or sevelamer hydrochloride in several experimental models. Lanthanum carbonate and aluminum hydroxide markedly increased excretion of [32P]-phosphate in feces and reduced excretion in urine in rats with normal renal function (p < 0.05), indicating good dietary phosphate-binding efficacy. In rats with chronic renal failure, lanthanum carbonate and aluminum hydroxide reduced urinary phosphate excretion to a greater degree and more rapidly than calcium carbonate, which in turn was more effective than sevelamer hydrochloride. The potential to induce adverse pharmacological effects was assessed systematically in mice, rats, and dogs with normal renal function using standard in vivo models. There was no evidence of any adverse secondary pharmacological effects of lanthanum carbonate on the central nervous, cardiovascular, respiratory, or gastrointestinal systems. These studies indicate that lanthanum carbonate is the more potent of the currently available dietary phosphate binders. No adverse secondary pharmacological actions were observed in vivo in a systematic evaluation at high doses. PMID:21332344

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.

[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.

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.

A review of the pharmacology and clinical efficacy of brivaracetam

PubMed Central

Klein, Pavel; Diaz, Anyzeila; Gasalla, Teresa; Whitesides, John

2018-01-01

Brivaracetam (BRV; Briviact) is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10–1,000 mg) and multiple (200–800 mg/day) oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50–200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic–clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug–drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV. PMID:29403319

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

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

Traditional Uses, Pharmacological Efficacy, and Phytochemistry of Moringa peregrina (Forssk.) Fiori. -A Review.

PubMed

Senthilkumar, Annadurai; Karuvantevida, Noushad; Rastrelli, Luca; Kurup, Shyam S; Cheruth, Abdul J

2018-01-01

Moringa is a sole genus of Moringaceae family with 13 species distributed in the tropical and sub-tropical regions. Among them, Moringa peregrina is one of the species which has wide range of traditional, nutritional, industrial, and medicinal values. The plant parts are used in folk medicine for many human health care purposes including diabetes, wound healing, disinfectant, fever, constipation, muscle pains, slimness, burns, labor pain, hypertension, malaria, stomach disorder, asthma, skin problems, and to expel a retained placenta. In addition to medicinal value, M. peregrina has cultural, spiritual, and religious connections with the native people of Arabian Peninsula. M. peregrina plant parts were tested for many pharmacological activities viz , antioxidant, anti-microbial, anti-diabetic, anti-spasmodic, hypertension, hepatotoxicity, lipid lowering activity, anti-inflammatory, anti-cancer, and memory disorders. Few active molecules belong to the class isothiocyanate, flavonoid, triterpenoid, phytosterol, polyphenol, and glycoside were also isolated, identified and reported for anti-microbial, anti-oxidant, anthelmintic, anti-mutagenic, neuroprotective, anti-cancer, anti-hypertensive, anti-diabetic, anti-infective, anti-allergic, anti-inflammatory, herbicidal, lipid lowering potential, anti-trypanosomal, and cytotoxic activities. So, the aim of the present review is to provide comprehensive information from recognized sources on the traditional uses, pharmacological efficacy and phytochemistry of the desert medicinal plant, M. peregrina . The information provided in this review will be very useful for further studies to develop novel therapeutic drugs.

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

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.

Statistical reporting of clinical pharmacology research.

PubMed

Ring, Arne; Schall, Robert; Loke, Yoon K; Day, Simon

2017-06-01

Research in clinical pharmacology covers a wide range of experiments, trials and investigations: clinical trials, systematic reviews and meta-analyses of drug usage after market approval, the investigation of pharmacokinetic-pharmacodynamic relationships, the search for mechanisms of action or for potential signals for efficacy and safety using biomarkers. Often these investigations are exploratory in nature, which has implications for the way the data should be analysed and presented. Here we summarize some of the statistical issues that are of particular importance in clinical pharmacology research. © 2017 The British Pharmacological Society.

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.

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.

Preoperative oral use of Ibuprofen or dexamethasone may improve the anesthetic efficacy of an inferior alveolar nerve block in patients diagnosed with irreversible pulpitis.

PubMed

Nusstein, John M

2013-09-01

Effect of premedication with ibuprofen and dexamethasone on success rate of inferior alveolar nerve block for teeth with asymptomatic irreversible pulpitis: a randomized clinical trial. Shahi S, Moktari H, Rahimi S, Yavari HR, Narimani S, Abdolrahmi M, Nezafati S. J Endod 2013;39(2):160-2. John M. Nusstein, DDS, MS PURPOSE/QUESTION: To determine whether preoperative oral administration of ibuprofen (400 mg), dexamethasone (0.5 mg), or placebo (lactose) would improve the anesthetic success rate of an inferior alveolar nerve block in patients with molars diagnosed with asymptomatic irreversible pulpitis University: Dental and Periodontal Research Center of Tabriz, Tabriz University of Medical Sciences, Tabriz, Iran Randomized controlled trial Level 2: Limited-quality, patient-oriented evidence Not applicable. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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

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.

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.

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.

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.

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

Tobacco Harms, Nicotine Pharmacology, and Pharmacologic Tobacco Cessation Interventions for Women.

PubMed

Baraona, L Kim; Lovelace, Dawn; Daniels, Julie L; McDaniel, Linda

2017-05-01

Firsthand and secondhand tobacco use is linked to a multitude of harmful illnesses, adverse perinatal outcomes, and death. Cessation attempts among women may be hampered by their unique biologic response to nicotine. Current research has revealed epigenetic changes from intrauterine nicotine exposure that have intergenerational consequences. Multiple studies have demonstrated the efficacy of various pharmacologic tobacco cessation interventions in conjunction with behavioral counseling. Based on this evidence, the US Preventative Services Task Force (USPSTF) 2015 guideline recommends pharmacologic therapy for all nonpregnant persons who smoke in addition to behavioral counseling. The effectiveness of pharmacologic treatments among pregnant women is less clear, with far fewer studies evaluating potential benefits and harms. While exposure to pharmacologic therapies raises concerns for fetal safety, these potential risks must be weighed against those of continued tobacco use, which guarantees fetal exposure to nicotine. First-line tobacco cessation medications include nicotine replacement therapy (NRT), bupropion, and varenicline. Second-line medications include nortriptyline and clonidine. Pharmacokinetics, effectiveness, regimens, and safety profiles for nonpregnant, pregnant, and lactating women are reviewed. Alternative tobacco cessation options and potential new pharmacologic tobacco cessation agents are discussed. Initiating brief interventions, using the 5A's and 5R's model is described. © 2017 by the American College of Nurse-Midwives.

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.

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

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.

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.

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.

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.

Comparative evaluation of ibuprofen/beta-cyclodextrin complexes obtained by supercritical carbon dioxide and other conventional methods.

PubMed

Hussein, Khaled; Türk, Michael; Wahl, Martin A

2007-03-01

The preparation of drug/cyclodextrin complexes is a suitable method to improve the dissolution of poor soluble drugs. The efficacy of the Controlled Particle Deposition (CPD) as a new developed method to prepare these complexes in a single stage process using supercritical carbon dioxide is therefore compared with other conventional methods. Ibuprofen/beta-cyclodextrin complexes were prepared with different techniques and characterized using FTIR-ATR spectroscopy, powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). In addition, the influences of the processing technique on the drug content (HPLC) and the dissolution behavior were studied. Employing the CPD-process resulted in a drug content of 2.8+/-0.22 wt.% in the carrier. The material obtained by CPD showed an improved dissolution rate of ibuprofen at pH 5 compared with the pure drug and its physical mixture with beta-cyclodextrin. In addition CPD material displays the highest dissolution (93.5+/- 2.89% after 75 min) compared to material obtained by co-precipitation (61.3 +/-0.52%) or freeze-drying (90.6 +/-2.54%). This study presents the CPD-technique as a well suitable method to prepare a drug/beta-cyclodextrin complex with improved drug dissolution compared to the pure drug and materials obtained by other methods.

Traditional Uses, Pharmacological Efficacy, and Phytochemistry of Moringa peregrina (Forssk.) Fiori. —A Review

PubMed Central

Senthilkumar, Annadurai; Karuvantevida, Noushad; Rastrelli, Luca; Kurup, Shyam S.; Cheruth, Abdul J.

2018-01-01

Moringa is a sole genus of Moringaceae family with 13 species distributed in the tropical and sub-tropical regions. Among them, Moringa peregrina is one of the species which has wide range of traditional, nutritional, industrial, and medicinal values. The plant parts are used in folk medicine for many human health care purposes including diabetes, wound healing, disinfectant, fever, constipation, muscle pains, slimness, burns, labor pain, hypertension, malaria, stomach disorder, asthma, skin problems, and to expel a retained placenta. In addition to medicinal value, M. peregrina has cultural, spiritual, and religious connections with the native people of Arabian Peninsula. M. peregrina plant parts were tested for many pharmacological activities viz, antioxidant, anti-microbial, anti-diabetic, anti-spasmodic, hypertension, hepatotoxicity, lipid lowering activity, anti-inflammatory, anti-cancer, and memory disorders. Few active molecules belong to the class isothiocyanate, flavonoid, triterpenoid, phytosterol, polyphenol, and glycoside were also isolated, identified and reported for anti-microbial, anti-oxidant, anthelmintic, anti-mutagenic, neuroprotective, anti-cancer, anti-hypertensive, anti-diabetic, anti-infective, anti-allergic, anti-inflammatory, herbicidal, lipid lowering potential, anti-trypanosomal, and cytotoxic activities. So, the aim of the present review is to provide comprehensive information from recognized sources on the traditional uses, pharmacological efficacy and phytochemistry of the desert medicinal plant, M. peregrina. The information provided in this review will be very useful for further studies to develop novel therapeutic drugs. PMID:29867473

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.

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.

Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus

PubMed Central

Oncel, Mehmet Yekta; Erdeve, Omer

2016-01-01

Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants which is inversely related to birth weight and gestational age. Cyclooxygenase inhibitors such as indomethacin and ibuprofen which block the prostaglandin conversion from arachidonic acid are the most commonly used drugs for ductal closure. This review focuses on the safety and efficacy oral medications in the management of PDA in preterm infants. Ibuprofen seems to be the first choice due to its higher safety profile, as it is associated with fewer gastrointestinal and renal side effects when compared to indomethacin. PDA closure rates are better with oral than with intravenous ibuprofen probably due to the pharmacokinetic of the drug. However, these medications were reported to be associated with several adverse including transient renal failure, gastrointestinal bleeding and perforation, hyperbilirubinemia and platelet dysfunction. Paracetamol seems be an alternative to PDA therapy with lower adverse events and side effects. PMID:26862505

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

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

Design of Block Copolymer Costabilized Nonionic Microemulsions and Their In Vitro and In Vivo Assessment as Carriers for Sustained Regional Delivery of Ibuprofen via Topical Administration.

PubMed

Djekic, Ljiljana; Martinovic, Martina; Stepanović-Petrović, Radica; Tomić, Maja; Micov, Ana; Primorac, Marija

2015-08-01

Nonionic surfactants (caprylocaproyl macrogol-8 glycerides, octoxynol-12, polysorbate-20, and polyethylene glycol-40 hydrogenated castor oil) (47.03%, w/w), costabilizer (poloxamer 407) (12%-20%, w/w), oil (isopropyl myristate) (5.22%, w/w), water (q.s. ad 100%, w/w), and ibuprofen (5%, w/w) were used to develop oil-in-water microemulsions with Newtonian flow behavior, low viscosity (from 368 ± 38 to 916 ± 46 mPa s), and average droplet size from 14.79 ± 0.31 to 16.54 ± 0.75 nm. Ibuprofen in vitro release from the microemulsions was in accordance with zero-order kinetics (R0(2) > 0.99) for at least 12 h. The maximum drug release rate (3.55%h(-1) ) was from the microemulsion M3 comprising 16%, w/w of poloxamer 407. The release rate of ibuprofen from the reference hydrogel followed Higuchi kinetics (RH(2) > 0.99), and drug amount released after the 6th hour was negligible. In a rat model of inflammation, the microemulsion M3 was significantly more efficacious than the reference hydrogel in exerting antihyperalgesic effects in prophylactic topical treatment, whereas they were comparable in therapeutic treatment as well as in producing antiedematous effect in both protocols. No obvious skin irritation was observed in in vivo studies. The developed nonionic surfactants-based microemulsions containing the optimal concentration of poloxamer 407 could be promising carriers for sustained regional delivery of ibuprofen via topical administration. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

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.

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

Development and pharmacological characterization of a model of sleep disruption-induced hypersensitivity in the rat.

PubMed

Wodarski, R; Schuh-Hofer, S; Yurek, D A; Wafford, K A; Gilmour, G; Treede, R-D; Kennedy, J D

2015-04-01

Sleep disturbance is a commonly reported co-morbidity in chronic pain patients, and conversely, disruption of sleep can cause acute and long-lasting hypersensitivity to painful stimuli. The underlying mechanisms of sleep disruption-induced pain hypersensitivity are poorly understood. Confounding factors of previous studies have been the sleep disruption protocols, such as the 'pedestal over water' or 'inverted flower pot' methods, that can cause large stress responses and therefore may significantly affect pain outcome measures. Sleep disruption was induced by placing rats for 8 h in a slowly rotating cylindrical cage causing arousal via the righting reflex. Mechanical (Von Frey filaments) and thermal (Hargreaves) nociceptive thresholds were assessed, and plasma corticosterone levels were measured (mass spectroscopy). Sleep disruption-induced hypersensitivity was pharmacologically characterized with drugs relevant for pain treatment, including gabapentin (30 mg/kg and 50 mg/kg), Ica-6p (Kv7.2/7.3 potassium channel opener; 10 mg/kg), ibuprofen (30 mg/kg and 100 mg/kg) and amitriptyline (10 mg/kg). Eight hours of sleep disruption caused robust mechanical and heat hypersensitivity in the absence of a measurable change in plasma corticosterone levels. Gabapentin had no effect on reduced nociceptive thresholds. Ibuprofen attenuated mechanical thresholds, while Ica-6p and amitriptyline attenuated only reduced thermal nociceptive thresholds. These results show that acute and low-stress sleep disruption causes mechanical and heat hypersensitivity in rats. Mechanical and heat hypersensitivity exhibited differential sensitivity to pharmacological agents, thus suggesting dissociable mechanisms for those two modalities. Ultimately, this model could help identify underlying mechanisms linking sleep disruption and hypersensitivity. © 2014 European Pain Federation - EFIC®

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

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.

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

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.

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

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.

Comparative efficacy and acceptability of pharmacological treatments for post-traumatic stress disorder in adults: a network meta-analysis.

PubMed

Cipriani, Andrea; Williams, Taryn; Nikolakopoulou, Adriani; Salanti, Georgia; Chaimani, Anna; Ipser, Jonathan; Cowen, Phil J; Geddes, John R; Stein, Dan J

2017-12-19

Guidelines about post-traumatic stress disorder (PTSD) recommend broad categories of drugs, but uncertainty remains about what pharmacological treatment to select among all available compounds. Cochrane Central Register of Controlled Trials register, MEDLINE, PsycINFO, National PTSD Center Pilots database, PubMed, trial registries, and databases of pharmaceutical companies were searched until February 2016 for double-blind randomised trials comparing any pharmacological intervention or placebo as oral therapy in adults with PTSD. Initially, we performed standard pairwise meta-analyses using a random effects model. We then carried out a network meta-analysis. The main outcome measures were mean change on a standardised scale and all-cause dropout rate. Acute treatment was defined as 8-week follow up. Desipramine, fluoxetine, paroxetine, phenelzine, risperidone, sertraline, and venlafaxine were more effective than placebo; phenelzine was better than many other active treatments and was the only drug, which was significantly better than placebo in terms of dropouts (odds ratio 7.50, 95% CI 1.72-32.80). Mirtazapine yielded a relatively high rank for efficacy, but the respective value for acceptability was not among the best treatments. Divalproex had overall the worst ranking. The efficacy and acceptability hierarchies generated by our study were robust against many sources of bias. The differences between drugs and placebo were small, with the only exception of phenelzine. Considering the small amount of available data, these results are probably not robust enough to suggest phenelzine as a drug of choice. However, findings from this review reinforce the idea that phenelzine should be prioritised in future trials in PTSD.

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

Does platelet mass influence the effectiveness of ibuprofen treatment for patent ductus arteriosus in preterm infants?

PubMed

Akar, Selahattin; Karadag, Nilgun; Gokmen Yildirim, Tulin; Toptan, Handan Hakyemez; Dincer, Emre; Tuten, Abdulhamit; Yavuz, Taner; Topcuoglu, Sevilay; Karatepe, Hande Ozgun; Ozalkaya, Elif; Karatekin, Guner; Ovali, Fahri

2016-12-01

The aim of this study is to evaluate whether the platelet mass in the first 24 h of life is effective on closure of patent ductus arteriosus (PDA) or not. Preterm infants with a gestational age of < 32 weeks, hospitalized at a tertiary neonatal intensive care unit (NICU) and requiring medical treatment (intravenous or oral ibuprofen) for hemodinamically significant PDA (hsPDA) were enrolled in this study. The patients were divided into two groups after first course of pharmacologic treatment according to closure of PDA (Group 1: PDA closure, Group 2: PDA without closure). Groups were compared in terms of demographics findings, morbidities, platelet measurements like counts, mean platelet volume (MPV) and platelet mass (platelet count × mean platelet volume). The study included 77 preterm newborns in Group 1, and 30 preterms in Group 2. There were no differences in birth weight, gestational age, gender and maternal risk factors between the study groups. The mean platelet count in the first postnatal blood count was in Group 1: 211.3 ± 89.2 × 10(3)/mm(3) and in Group 2: 216.5 ± 26 × 10(3)/mm(3), respectively (p = 0.783). The mean platelet volumes (MPV) were similar in both groups (p = 0.535). No statistically significant difference between platelet mass values was detected (Group 1: 1811 ± 884 fl/nl, Group 2: 1868 ± 717 fl/nl) (p = 0.753). Our data suggest that platelet count, MPV and platelet mass did not affect the closure of hsPDA with ibuprofen.

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.

Efficacy of preoperative ibuprofen on the success of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a randomized clinical trial.

PubMed

Noguera-Gonzalez, D; Cerda-Cristerna, B I; Chavarria-Bolaños, D; Flores-Reyes, H; Pozos-Guillen, A

2013-11-01

To evaluate the effect of preoperative oral ibuprofen (IBU) on the success of inferior alveolar nerve blocks (IANBs) with mepivacaine containing 1 : 100 000 epinephrine for patients with symptomatic irreversible pulpitis (SIP). The present study was a double-blind, randomized, placebo-controlled clinical trial. The study included two study groups each consisting of 25 patients who exhibited symptomatic irreversible pulpitis of a mandibular posterior tooth. The patients presented prolonged moderate or severe pain (>10 s) after cold testing and indicated their pain scores on a Heft-Parker visual analogue scale. The patients received identically appearing capsules containing either 600 mg IBU (IBUg) or gelatin (placebo, PLAg) 1 h before administration of IANB with 2% mepivacaine containing 1 : 100 000 epinephrine. After 15 min, the anaesthetic blockade was assessed by a three-step examination (lip numbness, positive/negative response to cold testing and clinical discomfort during endodontic access). IANB success was defined as the absence of pain during any of these evaluations. The data were analysed using the chi-squared test. All of the patients reported moderate or severe pain before the preoperative procedure. Statistically significant differences were observed between the IBUg and PLAg (P < 0.05); the success rates for the IANB were 72% (IBUg) and 36% (PLAg). Preoperative oral administration of IBU significantly improved the efficacy of IANB in patients with symptomatic irreversible pulpitis. © 2013 International Endodontic Journal. Published by John Wiley & Sons Ltd.

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

Pharmacological enhancement of behavioral therapy: focus on posttraumatic stress disorder.

PubMed

Choi, Dennis C; Rothbaum, Barbara O; Gerardi, Maryrose; Ressler, Kerry J

2010-01-01

Improved efficacy in the treatment of posttraumatic stress disorder (PTSD) and other anxiety disorders is urgently needed. Traditional anxiety treatments of hypnosis and psychodynamic therapy may be of some help, but uncontrolled studies lead to inconclusive results on the efficacy of these treatment techniques. There is a larger literature supporting the efficacy of cognitive-behavioral procedures with PTSD, including prolonged exposure therapy, eye movement desensitization and reprocessing, and anxiety management techniques. The cutting-edge technology of virtual reality-based exposure therapy for PTSD is particularly exciting. To further build on effective psychosocial treatments, current pharmacological augmentation approaches to emotional learning are being combined with psychotherapy. In particular, D-cycloserine, a partial NMDA agonist, has shown to be effective in facilitating the exposure/extinction therapy to improve the efficacy of treating anxiety disorders, and may guide the way for new pharmacological enhancements of behavioral therapy.

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.

[Non-Pharmacological Interventions for Pregnancy-Related Sleep Disturbances].

PubMed

Hung, Hsuan-Man; Chiang, Hsiao-Ching

2017-02-01

Most women experience the worse sleep quality of their life during pregnancy and the early postpartum period. Although pregnancy typically accounts for a relatively short part of a woman's life, the related sleep disturbances may have a significant and negative impact on her long-term health. Approximately 78-80% of pregnant women experience sleep disturbances, including interruptions in deep sleep, decreased total sleep time, poor subjective sleep quality, frequent night waking, and reduced sleep efficacy. Sleep disturbances during pregnancy start during the first trimester and become prevalent during the third trimester. Related factors include physiological and psychosocial changes and an unhealthy lifestyle. As non-pharmacological interventions have the potential to improve sleep quality in 70% to 80% of patients with insomnia, this is the main approached that is currently used to treat pregnancy-related sleep disturbances. Examples of these non-pharmacological interventions include music therapy, aerobic exercise, massage, progressive muscle relaxation, multi-modal interventions, and the use of a maternity support belt. The efficacy and safety of other related non-pharmacological interventions such as auricular acupressure, cognitive therapy, tai chi, and aromatherapy remain uncertain, with more empirical research required. Additionally, non-pharmacological interventions do not effectively treat sleep disturbances in all pregnant women.

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.

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

Efficacy and safety of pharmacological agents in the treatment of erythema migrans in early Lyme borreliosis-systematic review protocol.

PubMed

Torbahn, Gabriel; Hofmann, Heidelore; Allert, Roman; Freitag, Michael H; Dersch, Rick; Fingerle, Volker; Sommer, Harriet; Motschall, Edith; Meerpohl, Jörg J; Schmucker, Christine

2016-05-03

Erythema migrans represents an early cutaneous and most common manifestation of Lyme borreliosis. Recommendations regarding pharmacological agents, dose and duration of treatment are subject of intense debate. This review aims to explore differences in efficacy and safety between pharmacological treatments and control treatment. To identify relevant studies, we will conduct a systematic literature search. We will include randomised controlled trials (RCTs) and non-RCTs. Eligible comparative studies need to (1) consider patients with a diagnosis of erythema migrans resulting from Lyme borreliosis and (2) compare different pharmacological agents against each other, against any other non-pharmacological treatment, placebo or no treatment. Two review authors will independently assess included studies for risk of bias according to the methods of the Cochrane Handbook for Systematic Reviews of Interventions and related to specific study designs. We will address patient-relevant outcomes including clinical remission of cutaneous symptoms, any treatment-related adverse events, quality of life and progressive symptoms such as neuroborreliosis or Lyme carditis and flu-like symptoms. Provided that the identified trials are comparable in terms of clinical issues, combined estimates will be provided. Estimations of treatment effects will be calculated based on a random effects model. Heterogeneity will be evaluated based on I (2) and chi-square test. In case of significant heterogeneity, a pooled estimate will not be provided, but heterogeneity will be investigated on the basis of methodological and clinical study aspects. We plan subgroup analysis to reveal potential differences in the effect estimates between patient populations and treatment specifications. We will consider risk of bias using sensitivity analyses to decide whether to rely on the pooled estimates. The quality of a body of evidence for individual outcomes will be assessed using the GRADE approach. Benefits and

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.

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.

Celecoxib versus ibuprofen in the prevention of heterotopic ossification following total hip replacement: a prospective randomised trial.

PubMed

Saudan, M; Saudan, P; Perneger, T; Riand, N; Keller, A; Hoffmeyer, P

2007-02-01

We examined whether a selective cyclooxygenase-2 (COX-2) inhibitor (celecoxib) was as effective as a non-selective inhibitor (ibuprofen) for the prevention of heterotopic ossification following total hip replacement. A total of 250 patients were randomised to receive celecoxib (200 mg b/d) or ibuprofen (400 mg t.d.s) for ten days after surgery. Anteroposterior radiographs of the pelvis were examined for heterotopic ossification three months after surgery. Of the 250 patients, 240 were available for assessment. Heterotopic ossification was more common in the ibuprofen group (none 40.7% (50), Brooker class I 46.3% (57), classes II and III 13.0% (16)) than in the celecoxib group (none 59.0% (69), Brooker class I 35.9% (42), classes II and III 5.1% (6), p=0.002). Celecoxib was more effective than ibuprofen in preventing heterotopic bone formation after total hip replacement.

A Review of Pharmacologic Treatment for Compulsive Buying Disorder.

PubMed

Soares, Célia; Fernandes, Natália; Morgado, Pedro

2016-04-01

At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder.

Quetiapine and its metabolite norquetiapine: translation from in vitro pharmacology to in vivo efficacy in rodent models

PubMed Central

Widzowski, D; Maciag, C; Zacco, A; Hudzik, T; Liu, J; Nyberg, S; Wood, M W

2015-01-01

Background and Purpose Quetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major active metabolite, norquetiapine, has been shown to have a distinct in vitro pharmacological profile consistent with a broad therapeutic range and may contribute to the clinical profile of quetiapine. Experimental Approach We evaluated quetiapine and norquetiapine, using in vitro binding and functional assays of targets known to be associated with antidepressant and anxiolytic drug actions and compared these activities with a representative range of established antipsychotics and antidepressants. To determine how the in vitro pharmacological properties translate into in vivo activity, we used preclinical animal models with translational relevance to established antidepressant‐like and anxiolytic‐like drug action. Key Results Norquetiapine had equivalent activity to established antidepressants at the noradrenaline transporter (NET), while quetiapine was inactive. Norquetiapine was active in the mouse forced swimming and rat learned helplessness tests. In in vivo receptor occupancy studies, norquetiapine had significant occupancy at NET at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists at 5‐HT1A receptors, and the anxiolytic‐like activity of norquetiapine in rat punished responding was blocked by the 5‐HT1A antagonist, WAY100635. Conclusions and Implications Quetiapine and norquetiapine have multiple in vitro pharmacological actions, and results from preclinical studies suggest that activity at NET and 5‐HT1A receptors contributes to the antidepressant and anxiolytic effects in patients treated with quetiapine. PMID:26436896

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…

Non Pharmacological Cognitive Enhancers - Current Perspectives.

PubMed

Sachdeva, Ankur; Kumar, Kuldip; Anand, Kuljeet Singh

2015-07-01

Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms 'non pharmacological and cognitive' in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied.

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.

New approaches to the pharmacological treatment of obesity: can they break through the efficacy barrier?

PubMed

Kennett, G A; Clifton, P G

2010-11-01

In this review we assess the range of centrally active anorectics that are either in human clinical trials, or are likely to be so in the near future. We describe their weight loss efficacy, mode of action at both pharmacological and behavioural levels, where understood, together with the range of side effects that might be expected in clinical use. We have however evaluated these compounds against the considerably more rigorous criteria that are now being used by the Federal Drugs Agency and European Medicines Agency to decide approvals and market withdrawals. Several trends are evident. Recent advances in the understanding of energy balance control have resulted in the exploitation of a number of new targets, some of which have yielded promising data in clinical trials for weight loss. A second major trend is derived from the hypothesis that improved weight loss efficacy over current therapy is most likely to emerge from treatments targeting multiple mechanisms of energy balance control. This reasoning has led to the development of a number of new treatments for obesity where multiple mechanisms are targeted, either by a single molecule, such as tesofensine, or through drug combinations such as qnexa, contrave, empatic, and pramlintide+metreleptin. Many of these approaches also utilise advances in formulation technology to widen safety margins. Finally, the practicality of peptide therapies for obesity has become better validated in recent studies and this may allow more rapid exploitation of novel targets, rather than awaiting the development of orally available small molecules. We conclude that novel, more efficacious and better tolerated treatments for obesity may become available in the near future. Copyright © 2010 Elsevier Inc. All rights reserved.

[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.

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.

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

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.

The genus Caesalpinia L. (Caesalpiniaceae): phytochemical and pharmacological characteristics.

PubMed

Zanin, João L Baldim; de Carvalho, Bianca A; Martineli, Paloma Salles; dos Santos, Marcelo Henrique; Lago, João Henrique G; Sartorelli, Patrícia; Viegas, Cláudio; Soares, Marisi G

2012-06-29

The genus Caesalpinia (Caesalpiniaceae) has more than 500 species, many of which have not yet been investigated for potential pharmacological activity. Several classes of chemical compounds, such as flavonoids, diterpenes, and steroids, have been isolated from various species of the genus Caesalpinia. It has been reported in the literature that these species exhibit a wide range of pharmacological properties, including antiulcer, anticancer, antidiabetic, anti-inflammatory, antimicrobial, and antirheumatic activities that have proven to be efficacious in ethnomedicinal practices. In this review we present chemical and pharmacological data from recent phytochemical studies on various plants of the genus Caesalpinia.

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

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 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

Clinical pharmacology and efficacy of rotigotine (Neupro® patch) in the treatment of restless leg syndrome.

PubMed

Ferini-Strambi, Luigi; Marelli, Sara; Galbiati, Andrea

2016-08-01

Restless legs syndrome/Willis Ekbom disease (RLS/WED) is a sensorimotor disorder characterized by unpleasant sensations in the legs accompanied by an urge to move them, that typically occurs and tend to worsen in the evening/night or during period of inactivity. Standard medications for RLS/WED are dopamine agonists and calcium channel α-2-δ ligands. The clinical spectrum of RLS/WED is very broad, ranging from individuals suffering from the disease during limited periods up to those severely affected, with daily symptoms. In such cases a long-acting drug like rotigotine should be considered. The clinical pharmacology and efficacy of rotigotine was examined to evaluate the evidence supporting its use in RLS/WED. The rotigotine transdermal patch provides constant delivery of the drug, maintaining a stable plasma concentration over 24 hours by means of a single daily application. Several randomized, double-blind, placebo-controlled trials have demonstrated the efficacy of rotigotine in improving moderate-to-severe RLS/WED symptoms. Rotigotine is generally well tolerated. The most common adverse effects were application-site reactions, dose-dependent, more frequently reported in the first period of treatment. Incidence of augmentation in RLS/WED patients treated with oral dopamine agonists is higher when compared with the use of transdermal rotigotine.

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.

Clinical pharmacology and efficacy of sugammadex in the reversal of neuromuscular blockade.

PubMed

Schaller, Stefan Josef; Lewald, Heidrun

2016-09-01

Sugammadex is the first clinical representative of a class of drugs called steroidal muscle relaxant encapsulators. Due to its 1:1 binding of rocuronium or vecuronium, sugammadex can reverse any depth of neuromuscular block and has therefore revolutionized the way anesthetists think about drug reversal. This review gives an overview of the clinical pharmacology and efficacy of sugammadex in healthy patients as well as in patients with pre-existing diseases. After approval in Europe in 2008 and Asia in 2010, sugammadex has recently been approved in the USA and Canada. This will open the field for further research especially for the use in special patient populations and specific diseases. Due to its pharmacodynamic profile, sugammadex in combination with rocuronium might have the potential to displace succinylcholine as the gold standard muscle relaxant for rapid sequence inductions. The use of rocuronium or vecuronium with the potential to reverse its action with sugammadex seems to be safe in patients with impaired neuromuscular transmission, i.e. (neuro)muscular diseases including myasthenia gravis. Data from long-term use of sugammadex is not yet available. Evidence towards an economic advantage of using sugammadex, justifying the relatively high costs for an anesthesia-related drug, is missing.

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.

An evaluation of analgesic regimens for abdominal surgery in mice.

PubMed

Hayes, K E; Raucci, J A; Gades, N M; Toth, L A

2000-11-01

This study was designed to evaluate the efficacy of several analgesic regimens for use after intraperitoneal implantation of telemetry transmitters in mice. The lengths of time required for postoperative recovery of food and water intake, locomotor activity, and core temperature of mice that did not receive postsurgical analgesic medication were compared to those of mice that were given either an analgesic in the drinking water or buprenorphine injections. Many measured variables were not substantially altered by analgesic medications. However, ibuprofen-treated mice demonstrated significantly greater locomotor activity on days 2 through 5 after surgery and a more rapid return to stable postsurgical levels of activity and water intake as compared to those in untreated mice. These changes are consistent with potential analgesic efficacy of the ibuprofen treatment regimen. Buprenorphine injections elicited hyperactivity, hyperthermia, and reduced food and water intake during both the immediate postsurgical recovery period and after apparent recuperation from surgery, as compared to effects observed in saline-treated mice. Evaluating the effect of analgesic regimens on postsurgical changes in physiologic and behavioral variables can be useful in assessing the efficacy of analgesic treatments, but some changes may indicate pharmacologic effects that do not reflect pain relief.

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

Fesoterodine: Pharmacological properties and clinical implications.

PubMed

Gamé, Xavier; Peyronnet, Benoit; Cornu, Jean-Nicolas

2018-05-24

Fesoterodine (as one of three drugs: dutasteride, finasteride and fesoterodine) was classified B (beneficial) by LUTS-FORTA 2014, indicating that it is a medicinal product with proven or obvious efficacy in the elderly, with limited side effects and/or safety concerns. A systematic literature review was undertaken in January 2018 using the PubMed and Google Scholar databases with the following individual and combined keywords: "fesoterodine", "pharmacology", "overactive bladder" and "antimuscarinics". The aim of the review was to determine which of fesoterodine's pharmacological properties explains its clinical benefits in general patient populations with OAB and the elderly in particular. The articles in the results were then selected by publication language (English and French only), methodology (off-topic studies, reported cases and literature reviews were excluded), relevance to the subject matter and publication date prior to 31 January 2018. A total of 205 articles was initially obtained, with 115 read and 45 selected. It appears that the association of four pharmacological properties specific to fesoterodine can explain that this drug has a good balance between efficacy and tolerability. These properties are namely the drug's high and nearly equal affinity for both the M2 and M3 muscarinic receptors, poor penetration of the blood-brain barrier, lack of hepatic first-pass activation -fesoterodine being rapidly and extensively converted to its active metabolite, 5-hydroxymethyl tolterodine, by ubiquitous esterases-, and its extended-release formulation. Fesoterodine's pharmacological profile is optimal for the treatment of overactive bladder. It is now recognized as one of the leading first-line treatment for this indication. Copyright © 2018 Elsevier B.V. All rights reserved.

Efficacy of home-based non-pharmacological interventions for treating depression: a systematic review and network meta-analysis of randomised controlled trials

PubMed Central

Sukhato, Kanokporn; Lotrakul, Manote; Dellow, Alan; Ittasakul, Pichai; Thakkinstian, Ammarin; Anothaisintawee, Thunyarat

2017-01-01

Objectives To systematically review and compare the efficacy of all available home-based non-pharmacological treatments of depression. Design Systematic review and network meta-analysis of randomised controlled trials. Data sources Medline, Scopus and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases were searched since inceptions to 7 August 2016. Eligibility criteria Randomised controlled trials comparing the efficacy of home-based non-pharmacological interventions with usual care of patients with depression were included in the review. Main outcomes Depression symptom scores and disease remission rates at the end of treatment. Results Seventeen studies were included in the review. Home-based non-pharmacological interventions were categorised as (1) home-based psychological intervention, (2) home-based exercise intervention, (3) combined home-based psychological intervention with exercise intervention and (4) complementary medicine. Complementary medicine approaches were excluded from the meta-analysis due to heterogeneity. The standardised mean differences of post-treatment depression symptom scores between usual care groups and home-based psychological intervention, home-based exercise intervention and combined home-based psychological intervention with exercise intervention were −0.57 (95% CI −0.84 to −0.31), −1.03 (95% CI −2.89 to 0.82) and −0.78 (95% CI −1.09 to −0.47), respectively. These results suggest that only home-based psychological intervention and combined home-based psychological intervention with exercise intervention could significantly decrease depression scores. Compared with usual care groups, the disease remission rate was also significantly higher for home-based psychological intervention (pooled risk ratio=1.53; 95% CI 1.19 to 1.98) and combined home-based psychological intervention with exercise intervention (pooled risk ratio=3.47; 95% CI 2.11 to 5

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.

Association between Platelet Counts before and during Pharmacological Therapy for Patent Ductus Arteriosus and Treatment Failure in Preterm Infants.

PubMed

Sallmon, Hannes; Weber, Sven C; Dirks, Juliane; Schiffer, Tamara; Klippstein, Tamara; Stein, Anja; Felderhoff-Müser, Ursula; Metze, Boris; Hansmann, Georg; Bührer, Christoph; Cremer, Malte; Koehne, Petra

2018-01-01

The role of platelets for mediating closure of the ductus arteriosus in human preterm infants is controversial. Especially, the effect of low platelet counts on pharmacological treatment failure is still unclear. In this retrospective study of 471 preterm infants [<1,500 g birth weight (BW)], who were treated for a patent ductus arteriosus (PDA) with indomethacin or ibuprofen, we investigated whether platelet counts before or during pharmacological treatment had an impact on the successful closure of a hemodynamically significant PDA. The effects of other factors, such as sepsis, preeclampsia, gestational age, BW, and gender, were also evaluated. Platelet counts before initiation of pharmacological PDA treatment did not differ between infants with later treatment success or failure. However, we found significant associations between low platelet counts during pharmacological PDA therapy and treatment failure ( p  < 0.05). Receiver operating characteristic (ROC) curve analysis showed that platelet counts after the first, and before and after the second cyclooxygenase inhibitor (COXI) cycle were significantly associated with treatment failure (area under the curve of >0.6). However, ROC curve analysis did not reveal a specific platelet cutoff-value that could predict PDA treatment failure. Multivariate logistic regression analysis showed that lower platelet counts, a lower BW, and preeclampsia were independently associated with COXI treatment failure. We provide further evidence for an association between low platelet counts during pharmacological therapy for symptomatic PDA and treatment failure, while platelet counts before initiation of therapy did not affect treatment outcome.

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…

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

Impact of inhalational exposure to ethanol fuel on the pharmacokinetics of verapamil, ibuprofen and fluoxetine as in vivo probe drugs for CYP3A, CYP2C and CYP2D in rats.

PubMed

Cardoso, Juciane Lauren Cavalcanti; Lanchote, Vera Lucia; Pereira, Maria Paula Marques; Capela, Jorge Manuel Vieira; de Moraes, Natália Valadares; Lepera, José Salvador

2015-10-01

Occupational toxicology and clinical pharmacology integration will be useful to understand potential exposure-drug interaction and to shape risk assessment strategies in order to improve occupational health. The aim of the present study was to evaluate the effect of exposure to ethanol fuel on in vivo activities of cytochrome P450 (CYP) isoenzymes CYP3A, CYP2C and CYP2D by the oral administration of the probe drugs verapamil, ibuprofen and fluoxetine. Male Wistar rats exposed to filtered air or to 2000 ppm ethanol in a nose-only inhalation chamber during (6 h/day, 5 days/week, 6 weeks) received single oral doses of 10 mg/kg verapamil or 25 mg/kg ibuprofen or 10 mg/kg fluoxetine. The enantiomers of verapamil, norverapamil, ibuprofen and fluoxetine in plasma were analyzed by LC-MS/MS. The area under the curve plasma concentration versus time extrapolated to infinity (AUC(0-∞)) was calculated using the Gauss-Laguerre quadrature. Inhalation exposure to ethanol reduces the AUC of both verapamil (approximately 2.7 fold) and norverapamil enantiomers (>2.5 fold), reduces the AUC(0-∞) of (+)-(S)-IBU (approximately 2 fold) and inhibits preferentially the metabolism of (-)-(R)-FLU. In conclusion, inhalation exposure of ethanol at a concentration of 2 TLV-STEL (6 h/day for 6 weeks) induces CYP3A and CYP2C but inhibits CYP2D in rats. Copyright © 2015 Elsevier Ltd. All rights reserved.

Treatment of Pancreatic Cancer with Pharmacological Ascorbate

PubMed Central

Cieslak, John A.; Cullen, Joseph J.

2016-01-01

The prognosis for patients diagnosed with pancreatic cancer remains dismal, with less than 3% survival at 5 years. Recent studies have demonstrated that high-dose, intravenous pharmacological ascorbate (ascorbic acid, vitamin C) induces cytotoxicity and oxidative stress selectively in pancreatic cancer cells vs. normal cells, suggesting a promising new role of ascorbate as a therapeutic agent. At physiologic concentrations, ascorbate functions as a reducing agent and antioxidant. However, when pharmacological ascorbate is given intravenously, it is possible to achieve millimolar plasma concentration. At these pharmacological levels, and in the presence of catalytic metal ions, ascorbate can induce oxidative stress through the generation of hydrogen peroxide (H2O2). Recent in vitro and in vivo studies have demonstrated ascorbate oxidation occurs extracellularly, generating H2O2 flux into cells resulting in oxidative stress. Pharmacologic ascorbate also inhibits the growth of pancreatic tumor xenografts and displays synergistic cytotoxic effects when combined with gemcitabine in pancreatic cancer. Phase I trials of pharmacological ascorbate in pancreatic cancer patients have demonstrated safety and potential efficacy. In this chapter, we will review the mechanism of ascorbate-induced cytotoxicity, examine the use of pharmacological ascorbate in treatment and assess the current data supporting its potential as an adjuvant in pancreatic cancer. PMID:26201606

Pharmacological and non-pharmacological treatments for major depressive disorder: review of systematic reviews

PubMed Central

Gartlehner, Gerald; Wagner, Gernot; Matyas, Nina; Titscher, Viktoria; Greimel, Judith; Lux, Linda; Gaynes, Bradley N; Viswanathan, Meera; Patel, Sheila; Lohr, Kathleen N

2017-01-01

Objectives This study aims to summarise the evidence on more than 140 pharmacological and non-pharmacological treatment options for major depressive disorder (MDD) and to evaluate the confidence that patients and clinicians can have in the underlying science about their effects. Design This is a review of systematic reviews. Data sources This study used MEDLINE, Embase, Cochrane Library, PsycINFO and Epistemonikos from 2011 up to February 2017 for systematic reviews of randomised controlled trials in adult patients with acute-phase MDD. Methods We dually reviewed abstracts and full-text articles, rated the risk of bias of eligible systematic reviews and graded the strength of evidence. Results Nineteen systematic reviews provided data on 28 comparisons of interest. For general efficacy, only second-generation antidepressants were supported with high strength evidence, presenting small beneficial treatment effects (standardised mean difference: −0.35; 95% CI −0.31 to −0.38), and a statistically significantly higher rate of discontinuation because of adverse events than patients on placebo (relative risk (RR) 1.88; 95% CI 1.0 to 3.28). Only cognitive behavioural therapy is supported by reliable evidence (moderate strength of evidence) to produce responses to treatment similar to those of second-generation antidepressants (45.5% vs 44.2%; RR 1.10; 95% CI 0.93 to 1.30). All remaining comparisons of non-pharmacological treatments with second-generation antidepressants either led to inconclusive results or had substantial methodological shortcomings (low or insufficient strength of evidence). Conclusions In contrast to pharmacological treatments, the majority of non-pharmacological interventions for treating patients with MDD are not evidence based. For patients with strong preferences against pharmacological treatments, clinicians should focus on therapies that have been compared directly with antidepressants. Trial registration number International

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

Survey on treatments for primary headaches in 13 specialized juvenile Headache Centers: The first multicenter Italian study.

PubMed

Toldo, Irene; Rattin, Martina; Perissinotto, Egle; De Carlo, Debora; Bolzonella, Barbara; Nosadini, Margherita; Rossi, Livia Nicoletta; Vecchio, Angelo; Simonati, Alessandro; Carotenuto, Marco; Scalas, Cinzia; Sciruicchio, Vittorio; Raieli, Vincenzo; Mazzotta, Giovanni; Tozzi, Elisabetta; Valeriani, Massimiliano; Cianchetti, Carlo; Balottin, Umberto; Guidetti, Vincenzo; Sartori, Stefano; Battistella, Pier Antonio

2017-05-01

The purpose of this retrospective multicenter study was to evaluate the use and the self-perceived efficacy and tolerability of pharmacological and non-pharmacological treatments in children and adolescents with primary headaches. Study of a cohort of children and adolescents diagnosed with primary headache, consecutively referred to 13 juvenile Italian Headache Centers. An ad hoc questionnaire was used for clinical data collection. Among 706 patients with primary headaches included in the study, 637 cases with a single type of headache (migraine 76% - with and without aura in 10% and 67% respectively; tension-type headache 24%) were selected (mean age at clinical interview: 12 years). Acetaminophen and non-steroidal anti-inflammatory drugs (in particular ibuprofen) were commonly used to treat attacks, by 76% and 46% of cases respectively. Triptans were used overall by 6% of migraineurs and by 13% of adolescents with migraine, with better efficacy than acetaminophen and non-steroidal anti-inflammatory drugs. Preventive drugs were used by 19% of migraineurs and by 3% of subjects with tension-type headache. In migraineurs, flunarizine was the most frequently used drug (18%), followed by antiepileptic drugs (7%) and pizotifen (6%), while cyproheptadine, propanolol and amitriptyline were rarely used. Pizotifen showed the best perceived efficacy and tolerability. Melatonin and nutraceuticals were used by 10% and 32% of subjects, respectively, both for migraine and tension-type headache, with good results in terms of perceived efficacy and tolerability. Non-pharmacological preventive treatments (i.e. relaxation techniques, biofeedback, cognitive-behavioral therapy, acupuncture) were used only by 10% of cases (migraine 9%, tension-type headache 15%). Non-steroidal anti-inflammatory drugs, especially ibuprofen, should be preferred to acetaminophen for acute attacks of migraine or tension-type headache, because they were usually more effective and well tolerated. Triptans

Non Pharmacological Cognitive Enhancers – Current Perspectives

PubMed Central

Kumar, Kuldip; Anand, Kuljeet Singh

2015-01-01

Cognition refers to the mental processes involved in thinking, knowing, remembering, judging, and problem solving. Cognitive dysfunctions are an integral part of neuropsychiatric disorders as well as in healthy ageing. Cognitive Enhancers are molecules that help improve aspects of cognition like memory, intelligence, motivation, attention and concentration. Recently, Non Pharmacological Cognitive Enhancers have gained popularity as effective and safe alternative to various established drugs. Many of these Non Pharmacological Cognitive Enhancers seem to be more efficacious compared to currently available Pharmacological Cognitive Enhancers. This review describes and summarizes evidence on various Non Pharmacological Cognitive Enhancers such as physical exercise, sleep, meditation and yoga, spirituality, nutrients, computer training, brain stimulation, and music. We also discuss their role in ageing and different neuro-psychiatric disorders, and current status of Cochrane database recommendations. We searched the Pubmed database for the articles and reviews having the terms ‘non pharmacological and cognitive’ in the title, published from 2000 till 2014. A total of 11 results displayed, out of which 10 were relevant to the review. These were selected and reviewed. Appropriate cross-references within the articles along with Cochrane reviews were also considered and studied. PMID:26393186

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.

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

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.

The cubic ternary complex receptor-occupancy model. III. resurrecting efficacy.

PubMed

Weiss, J M; Morgan, P H; Lutz, M W; Kenakin, T P

1996-08-21

Early work in pharmacology characterized the interaction of receptors and ligands in terms of two parameters, affinity and efficacy, an approach we term the bipartite view. A precise formulation of efficacy only exists for very simple pharmacological models. Here we extend the notion of efficacy to models that incorporate receptor activation and G-protein coupling. Using the cubic ternary complex model, we show that efficacy is not purely a property of the ligand-receptor interaction; it also depends upon the distributional details of the receptor species in the native receptor ensemble. This suggests a distinction between what we call potential efficacy (a vector) and realized efficacy (a scalar). To each receptor species in the native receptor ensemble we assign a part-worth utility; taken together these utilities comprise the potential efficacy vector. Realized efficacy is the expectation of these part-worth utilities with respect to the frequency distribution of receptor species in the native receptor ensemble. In the parlance of statistical decision theory, the binding of a ligand to a receptor ensemble is a random prospect and realized efficacy is the utility of this prospect. We explore the implications that our definition of efficacy has for understanding agonism and in assessing the legitimacy of the bipartite view in pharmacology.

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.

Randomised clinical trial: gastrointestinal events in arthritis patients treated with celecoxib, ibuprofen or naproxen in the PRECISION trial.

PubMed

Yeomans, N D; Graham, D Y; Husni, M E; Solomon, D H; Stevens, T; Vargo, J; Wang, Q; Wisniewski, L M; Wolski, K E; Borer, J S; Libby, P; Lincoff, A M; Lüscher, T F; Bao, W; Walker, C; Nissen, S E

2018-06-01

To evaluate GI safety of celecoxib compared with 2 nonselective (ns) NSAIDs, as a secondary objective of a large trial examining multiorgan safety. This randomised, double-blind controlled trial analysed 24 081 patients. Osteoarthritis or rheumatoid arthritis patients, needing ongoing NSAID treatment, were randomised to receive celecoxib 100-200 mg b.d., ibuprofen 600-800 mg t.d.s. or naproxen 375-500 mg b.d. plus esomeprazole, and low-dose aspirin or corticosteroids if already prescribed. Clinically significant GI events (CSGIE-bleeding, obstruction, perforation events from stomach downwards or symptomatic ulcers) and iron deficiency anaemia (IDA) were adjudicated blindly. Mean treatment and follow-up durations were 20.3 and 34.1 months. While on treatment or 30 days after, CSGIE occurred in 0.34%, 0.74% and 0.66% taking celecoxib, ibuprofen and naproxen. Hazard ratios (HR) were 0.43 (95% CI 0.27-0.68, P = 0.0003) celecoxib vs ibuprofen and 0.51 (0.32-0.81, P = 0.004) vs naproxen. There was also less IDA on celecoxib: HR 0.43 (0.27-0.68, P = 0.0003) vs ibuprofen; 0.40 (0.25-0.62, P < 0.0001) vs naproxen. Even taken with low-dose aspirin, fewer CSGIE occurred on celecoxib than ibuprofen (HR 0.52 [0.29-0.94], P = 0.03), and less IDA vs naproxen (0.42 [0.23-0.77, P = 0.005]). Corticosteroid use increased total GI events and CSGIE. H. pylori serological status had no influence. Arthritis patients taking NSAIDs plus esomeprazole have infrequent clinically significant gastrointestinal events. Co-prescribed with esomeprazole, celecoxib has better overall GI safety than ibuprofen or naproxen at these doses, despite treatment with low-dose aspirin or corticosteroids. © 2018 John Wiley & Sons Ltd.

[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.

Acute over-the-counter pharmacological intervention does not adversely affect behavioral outcome following diffuse traumatic brain injury in the mouse.

PubMed

Harrison, Jordan L; Rowe, Rachel K; O'Hara, Bruce F; Adelson, P David; Lifshitz, Jonathan

2014-09-01

Following mild traumatic brain injury (TBI), patients may self-treat symptoms of concussion, including post-traumatic headache, taking over-the-counter (OTC) analgesics. Administering one dose of OTC analgesics immediately following experimental brain injury mimics the at-home treated population of concussed patients and may accelerate the understanding of the relationship between brain injury and OTC pharmacological intervention. In the current study, we investigate the effect of acute administration of OTC analgesics on neurological function and cortical cytokine levels after experimental diffuse TBI in the mouse. Adult, male C57BL/6 mice were injured using a midline fluid percussion (mFPI) injury model of concussion (6-10 min righting reflex time for brain-injured mice). Experimental groups included mFPI paired with either ibuprofen (60 mg/kg, i.p.; n = 16), acetaminophen (40 mg/kg, i.p.; n = 9), or vehicle (15% ethanol (v/v) in 0.9% saline; n = 13) and sham injury paired OTC medicine or vehicle (n = 7-10 per group). At 24 h after injury, functional outcome was assessed using the rotarod task and a modified neurological severity score. Following behavior assessment, cortical cytokine levels were measured by multiplex ELISA at 24 h post-injury. To evaluate efficacy on acute inflammation, cortical cytokine levels were measured also at 6 h post-injury. In the diffuse brain-injured mouse, immediate pharmacological intervention did not attenuate or exacerbate TBI-induced functional deficits. Cortical cytokine levels were affected by injury, time, or their interaction. However, levels were not affected by treatment at 6 or 24 h post-injury. These data indicate that acute administration of OTC analgesics did not exacerbate or attenuate brain-injury deficits which may inform clinical recommendations for the at-home treated mildly concussed patient.

Pharmacological interventions for pain relief during orthodontic treatment.

PubMed

Monk, Aoife B; Harrison, Jayne E; Worthington, Helen V; Teague, Annabel

2017-11-28

rating scale (NRS) or categorical scale. Two review authors independently screened the search results, agreed the studies to be included and extracted information from the included studies regarding methods, participants, interventions, outcomes, harms and results. We planned to resolve any discrepancies or disagreements through discussion. We used the Cochrane 'Risk of bias' tool to assess the risk of bias in the studies. We identified 32 relevant RCTs, which included 3110 participants aged 9 to 34 years, 2348 of whom we were able to include in our analyses. Seventeen of the studies had more than two arms. We were able to use data from 12 trials in meta-analyses that compared analgesics versus control (no treatment or a placebo); nine that compared non-steroidal anti-inflammatories (NSAIDs) versus paracetamol; and two that compared pre-emptive versus post-treatment ibuprofen for pain control following orthodontic treatment. One study provided data for the comparison of NSAIDs versus local anaesthetic.We found moderate-quality evidence that analgesics effectively reduced pain following orthodontic treatment when compared to no treatment or a placebo at 2 hours (mean difference (MD) -11.66 mm on a 0 to 100 mm VAS, 95% confidence interval (CI) -16.15 to -7.17; 10 studies, 685 participants), 6 hours (MD -24.27 mm on a VAS, 95% CI -31.44 to -17.11; 9 studies, 535 participants) and 24 hours (MD -21.19 mm on a VAS, 95% CI -28.31 to -14.06; 12 studies, 1012 participants).We did not find any evidence of a difference in efficacy between NSAID and paracetamol at 2, 6 or 24 hours (at 24 hours: MD -0.51, 95% CI -8.93 to 7.92; 9 studies, 734 participants; low-quality evidence).Very low-quality evidence suggested pre-emptive ibuprofen gave better pain relief at 2 hours than ibuprofen taken post treatment (MD -11.30, 95% CI -16.27 to -6.33; one study, 41 participants), however, the difference was no longer significant at 6 or 24 hours.A single study of 48 participants compared topical

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.

Simultaneous determination of 20 pharmacologically active substances in cow's milk, goat's milk, and human breast milk by gas chromatography-mass spectrometry.

PubMed

Azzouz, Abdelmonaim; Jurado-Sánchez, Beatriz; Souhail, Badredine; Ballesteros, Evaristo

2011-05-11

This paper reports a systematic approach to the development of a method that combines continuous solid-phase extraction and gas chromatography-mass spectrometry for the simultaneous determination of 20 pharmacologically active substances including antibacterials (chloramphenicol, florfenicol, pyrimethamine, thiamphenicol), nonsteroideal anti-inflammatories (diclofenac, flunixin, ibuprofen, ketoprofen, naproxen, mefenamic acid, niflumic acid, phenylbutazone), antiseptic (triclosan), antiepileptic (carbamazepine), lipid regulator (clofibric acid), β-blockers (metoprolol, propranolol), and hormones (17α-ethinylestradiol, estrone, 17β-estradiol) in milk samples. The sample preparation procedure involves deproteination of the milk, followed by sample enrichment and cleanup by continuous solid-phase extraction. The proposed method provides a linear response over the range of 0.6-5000 ng/kg and features limits of detection from 0.2 to 1.2 ng/kg depending on the particular analyte. The method was successfully applied to the determination of pharmacologically active substance residues in food samples including whole, raw, half-skim, skim, and powdered milk from different sources (cow, goat, and human breast).

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.

The Pharmacological Basis of Cannabis Therapy for Epilepsy.

PubMed

Reddy, Doodipala Samba; Golub, Victoria M

2016-04-01

Recently, cannabis has been suggested as a potential alternative therapy for refractory epilepsy, which affects 30% of epilepsy, both adults and children, who do not respond to current medications. There is a large unmet medical need for new antiepileptics that would not interfere with normal function in patients with refractory epilepsy and conditions associated with refractory seizures. The two chief cannabinoids are Δ-9-tetrahyrdrocannabinol, the major psychoactive component of marijuana, and cannabidiol (CBD), the major nonpsychoactive component of marijuana. Claims of clinical efficacy in epilepsy of CBD-predominant cannabis or medical marijuana come mostly from limited studies, surveys, or case reports. However, the mechanisms underlying the antiepileptic efficacy of cannabis remain unclear. This article highlights the pharmacological basis of cannabis therapy, with an emphasis on the endocannabinoid mechanisms underlying the emerging neurotherapeutics of CBD in epilepsy. CBD is anticonvulsant, but it has a low affinity for the cannabinoid receptors CB1 and CB2; therefore the exact mechanism by which it affects seizures remains poorly understood. A rigorous clinical evaluation of pharmaceutical CBD products is needed to establish the safety and efficacy of their use in the treatment of epilepsy. Identification of mechanisms underlying the anticonvulsant efficacy of CBD is also critical for identifying other potential treatment options. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

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

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.

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

A randomized controlled trial comparing acetaminophen plus ibuprofen versus acetaminophen plus codeine plus caffeine after outpatient general surgery.

PubMed

Mitchell, Alex; van Zanten, Sander Veldhuyzen; Inglis, Karen; Porter, Geoffrey

2008-03-01

Narcotics are used extensively in outpatient general surgery but are often poorly tolerated with variable efficacy. Acetaminophen combined with NSAIDs is a possible alternative. The objective of this study was to compare the efficacy of acetaminophen, codeine, and caffeine (Tylenol No. 3) with acetaminophen and ibuprofen for management of pain after outpatient general surgery procedures. A double-blind randomized controlled trial was performed in patients undergoing outpatient inguinal/umbilical/ventral hernia repair or laparoscopic cholecystectomy. Patients were randomized to receive acetaminophen plus codeine plus caffeine (Tylenol No. 3) or acetaminophen plus ibuprofen (AcIBU) 4 times daily for 7 days or until pain-free. Pain intensity, measured four times daily by visual analogue scale, was the primary outcome. Secondary end points included incidence of side effects, patient satisfaction, number of days until patient was pain-free, and use of alternative analgesia. One hundred forty-six patients were randomized (74 Tylenol No. 3 and 72 AcIBU), and 139 (95%) patients completed the study. No significant differences in mean or maximum daily visual analogue scale scores were identified between the 2 groups, except on postoperative day 2, when pain was improved in AcIBU patients (p = 0.025). During the entire week, mean visual analogue scale score was modestly lower in AcIBU patients (p = 0.018). More patients in the AcIBU group, compared with Tylenol No. 3, were satisfied with their analgesia (83% versus 64%, respectively; p = 0.02). There were more side effects with Tylenol No. 3 (57% versus 41%, p = 0.045), and the discontinuation rate was also higher in Tylenol No. 3-treated patients (11% versus 3%, p = 0.044). When compared with Tylenol No. 3, AcIBU was not an inferior analgesic and was associated with fewer side effects and higher patient satisfaction. AcIBU is an effective, low-cost, and safe alternative to codeine-based narcotic analgesia for outpatient

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

The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials

PubMed Central

Hutton, Brian; Núñez-Beltrán, Amparo; Page, Matthew J.; Ridao, Manuel; Macías Saint-Gerons, Diego; Catalá, Miguel A.; Tabarés-Seisdedos, Rafael; Moher, David

2017-01-01

Background Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. Methods and findings We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants

The pharmacological and non-pharmacological treatment of attention deficit hyperactivity disorder in children and adolescents: A systematic review with network meta-analyses of randomised trials.

PubMed

Catalá-López, Ferrán; Hutton, Brian; Núñez-Beltrán, Amparo; Page, Matthew J; Ridao, Manuel; Macías Saint-Gerons, Diego; Catalá, Miguel A; Tabarés-Seisdedos, Rafael; Moher, David

2017-01-01

Attention deficit hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in childhood. A wide variety of treatments have been used for the management of ADHD. We aimed to compare the efficacy and safety of pharmacological, psychological and complementary and alternative medicine interventions for the treatment of ADHD in children and adolescents. We performed a systematic review with network meta-analyses. Randomised controlled trials (≥ 3 weeks follow-up) were identified from published and unpublished sources through searches in PubMed and the Cochrane Library (up to April 7, 2016). Interventions of interest were pharmacological (stimulants, non-stimulants, antidepressants, antipsychotics, and other unlicensed drugs), psychological (behavioural, cognitive training and neurofeedback) and complementary and alternative medicine (dietary therapy, fatty acids, amino acids, minerals, herbal therapy, homeopathy, and physical activity). The primary outcomes were efficacy (treatment response) and acceptability (all-cause discontinuation). Secondary outcomes included discontinuation due to adverse events (tolerability), as well as serious adverse events and specific adverse events. Random-effects Bayesian network meta-analyses were conducted to obtain estimates as odds ratios (ORs) with 95% credibility intervals. We analysed interventions by class and individually. 190 randomised trials (52 different interventions grouped in 32 therapeutic classes) that enrolled 26114 participants with ADHD were included in complex networks. At the class level, behavioural therapy (alone or in combination with stimulants), stimulants, and non-stimulant seemed significantly more efficacious than placebo. Behavioural therapy in combination with stimulants seemed superior to stimulants or non-stimulants. Stimulants seemed superior to behavioural therapy, cognitive training and non-stimulants. Behavioural therapy, stimulants and their combination showed the

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

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.

2-(4-(Biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52) – a novel type of 5-lipoxygenase inhibitor with favourable molecular pharmacology and efficacy in vivo

PubMed Central

Greiner, C; Hörnig, C; Rossi, A; Pergola, C; Zettl, H; Schubert-Zsilavecz, M; Steinhilber, D; Sautebin, L; Werz, O

2011-01-01

BACKGROUND AND PURPOSE 5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of pro-inflammatory leukotrienes (LTs) representing a potential target for pharmacological intervention with inflammation and allergic disorders. Although many LT synthesis inhibitors are effective in simple in vitro test systems, they frequently fail in vivo due to lack of efficacy. Here, we attempted to assess the pharmacological potential of the previously identified 5-LO inhibitor 2-(4-(biphenyl-4-ylamino)-6-chloropyrimidin-2-ylthio)octanoic acid (HZ52). EXPERIMENTAL APPROACH We evaluated the efficacy of HZ52 in vivo using carrageenan-induced pleurisy in rats and platelet-activating factor (PAF)-induced lethal shock in mice. We also characterized 5-LO inhibition by HZ52 at the cellular and molecular level in comparison with other types of 5-LO inhibitor, that is, BWA4C, ZM230487 and hyperforin. KEY RESULTS HZ52, 1.5 mg·kg−1 i.p., prevented carrageenan-induced pleurisy accompanied by reduced LTB4 levels and protected mice (10 mg·kg−1, i.p.) against PAF-induced shock. Detailed analysis in cell-based and cell-free assays revealed that inhibition of 5-LO by HZ52 (i) does not depend on radical scavenging properties and is reversible; (ii) is not impaired by an increased peroxide tone or by elevated substrate concentrations; and (iii) is little affected by the cell stimulus or by phospholipids, glycerides, membranes or Ca2+. CONCLUSIONS AND IMPLICATIONS HZ52 is a promising new type of 5-LO inhibitor with efficacy in vivo and with a favourable pharmacological profile. It possesses a unique 5-LO inhibitory mechanism different from classical 5-LO inhibitors and seemingly lacks the typical disadvantages of former classes of LT synthesis blockers. PMID:21506958

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.

[PHYSIOLOGY AND PHARMACOLOGICAL PROPERTIES OF NANOMATERIALS].

PubMed

Chekman, I S

2015-01-01

Literature data and results of our department studies on theoretical and practical basics of nanoscience were summarized in the article. Much attention is paid to research in the field of physical, chemical, biological, medical, physiological, pharmacological, and toxicological properties of nanomaterials with the aim of their wider implementation into practice lately. The discovery of new quantum/wave properties of nanoparticles is of particular importance. The author of the article advances an idea: wave properties of nanomaterials play greater role with a decrease in particle size. The preponderance of wave properties compared with corpuscular ones in nanostructures determines a great change in their physical. chemical properties and an increase in physical, mechanical biological, physiological, pharmacological, and toxicologica activity. The idea advanced in the article hasn't been verified by theoretical or experimental studies for now. Joined efforts of scientists of different scientific fields are needed. A confirmation of hypothesis by specific findings will be of great importance for physiology, medicine, pharmacology and promote an implementation of new efficacious preparations into clinical practice. New fundamental discoveries could be made only by multidisciplinary approach.

Pharmacological chaperoning: a primer on mechanism and pharmacology.

PubMed

Leidenheimer, Nancy J; Ryder, Katelyn G

2014-05-01

Approximately forty percent of diseases are attributable to protein misfolding, including those for which genetic mutation produces misfolding mutants. Intriguingly, many of these mutants are not terminally misfolded since native-like folding, and subsequent trafficking to functional locations, can be induced by target-specific, small molecules variably termed pharmacological chaperones, pharmacoperones, or pharmacochaperones (PCs). PC targets include enzymes, receptors, transporters, and ion channels, revealing the breadth of proteins that can be engaged by ligand-assisted folding. The purpose of this review is to provide an integrated primer of the diverse mechanisms and pharmacology of PCs. In this regard, we examine the structural mechanisms that underlie PC rescue of misfolding mutants, including the ability of PCs to act as surrogates for defective intramolecular interactions and, at the intermolecular level, overcome oligomerization deficiencies and dominant negative effects, as well as influence the subunit stoichiometry of heteropentameric receptors. Not surprisingly, PC-mediated structural correction of misfolding mutants normalizes interactions with molecular chaperones that participate in protein quality control and forward-trafficking. A variety of small molecules have proven to be efficacious PCs and the advantages and disadvantages of employing orthostatic antagonists, active-site inhibitors, orthostatic agonists, and allosteric modulator PCs are considered. Also examined is the possibility that several therapeutic agents may have unrecognized activity as PCs, and this chaperoning activity may mediate/contribute to therapeutic action and/or account for adverse effects. Lastly, we explore evidence that pharmacological chaperoning exploits intrinsic ligand-assisted folding mechanisms. Given the widespread applicability of PC rescue of mutants associated with protein folding disorders, both in vitro and in vivo, the therapeutic potential of PCs is vast

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

A meta-analysis to determine the effect of pharmacological and non-pharmacological treatments on fibromyalgia symptoms comprising OMERACT-10 response criteria.

PubMed

Papadopoulou, Despoina; Fassoulaki, Argyro; Tsoulas, Christos; Siafaka, Ioanna; Vadalouca, Athina

2016-03-01

Fibromyalgia is characterized by widespread pain, sleep problems, fatigue, functional impairment, psychological distress, and cognitive dysfunction. The objective of this meta-analysis is to synthesize the available data on the effectiveness of pharmacological and non-pharmacological interventions across all domains included in the Outcome Measures in Rheumatology Clinical Trials (OMERACT-10) fibromyalgia response definitions, and to examine response based on these definitions. We searched Cochrane, PubMed, Scopus, and the reference lists of articles for randomized controlled trials of any drug formulation or non-pharmacological intervention used for fibromyalgia treatment. We extracted efficacy data regarding pain, sleep, physical function, fatigue, anxiety, depression, and cognition. The available data were insufficient to draw definite conclusions regarding response. Indirect evidence indicates that it may be expected with the use of serotonin noradrenaline reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NRIs), and multidisciplinary treatment.

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

Pharmacological treatment of anxiety disorders: Current treatments and future directions✩

PubMed Central

Farach, Frank J.; Pruitt, Larry D.; Jun, Janie J.; Jerud, Alissa B.; Zoellner, Lori A.; Roy-Byrne, Peter P.

2012-01-01

Modern pharmacological treatments for anxiety disorders are safer and more tolerable than they were 30 years ago. Unfortunately, treatment efficacy and duration have not improved in most cases despite a greater understanding of the pathophysiology of anxiety. Moreover, innovative treatments have not reached the market despite billions of research dollars invested in drug development. In reviewing the literature on current treatments, we argue that evidence-based practice would benefit from better research on the causes of incomplete treatment response as well as the comparative efficacy of drug combinations and sequencing. We also survey two broad approaches to the development of innovative anxiety treatments: the continued development of drugs based on specific neuroreceptors and the pharmacological manipulation of fear-related memory. We highlight directions for future research, as neither of these approaches is ready for routine clinical use. PMID:23023162

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.

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.

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].

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

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.

Tri-partite complex for axonal transport drug delivery achieves pharmacological effect

PubMed Central

2010-01-01

Background Targeted delivery of pharmaceutical agents into selected populations of CNS (Central Nervous System) neurons is an extremely compelling goal. Currently, systemic methods are generally used for delivery of pain medications, anti-virals for treatment of dermatomal infections, anti-spasmodics, and neuroprotectants. Systemic side effects or undesirable effects on parts of the CNS that are not involved in the pathology limit efficacy and limit clinical utility for many classes of pharmaceuticals. Axonal transport from the periphery offers a possible selective route, but there has been little progress towards design of agents that can accomplish targeted delivery via this intraneural route. To achieve this goal, we developed a tripartite molecular construction concept involving an axonal transport facilitator molecule, a polymer linker, and a large number of drug molecules conjugated to the linker, then sought to evaluate its neurobiology and pharmacological behavior. Results We developed chemical synthesis methodologies for assembling these tripartite complexes using a variety of axonal transport facilitators including nerve growth factor, wheat germ agglutinin, and synthetic facilitators derived from phage display work. Loading of up to 100 drug molecules per complex was achieved. Conjugation methods were used that allowed the drugs to be released in active form inside the cell body after transport. Intramuscular and intradermal injection proved effective for introducing pharmacologically effective doses into selected populations of CNS neurons. Pharmacological efficacy with gabapentin in a paw withdrawal latency model revealed a ten fold increase in half life and a 300 fold decrease in necessary dose relative to systemic administration for gabapentin when the drug was delivered by axonal transport using the tripartite vehicle. Conclusion Specific targeting of selected subpopulations of CNS neurons for drug delivery by axonal transport holds great promise

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.

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 use of monoamine pharmacological agents in the treatment of sexual dysfunction: evidence in the literature.

PubMed

Moll, Jennifer L; Brown, Candace S

2011-04-01

The monoamine neurotransmitters serotonin, dopamine, and norepinephrine play an important role in many medical and psychological conditions, including sexual responsiveness and behavior. Pharmacological agents that modulate monoamines may help alleviate sexual dysfunction. To provide an overview of pharmacological agents that modulate monoamines and their use in the treatment of sexual dysfunction. EMBASE and PubMed search for articles published between 1950 and 2010 using key words "sexual dysfunction,"monoamines,"monoaminergic receptors," and "generic names for pharmacological agents." To assess the literature evaluating the efficacy of monoamine pharmacologic agents used in the treatment of sexual dysfunction. The literature primarily cites the use of monoaminergic agents to treat sexual side effects from serotonergic reuptake inhibitors (SSRIs), with bupropion, buspirone and ropinirole providing the most convincing evidence. Controlled trials have shown that bupropion improves overall sexual dysfunction, but not frequency of sexual activity in depressed and nondepressed patients. Nefazodone and apomorphine have been used to treat sexual dysfunction, but their use is limited by significant side effect and safety profiles. New research on pharmacologic agents with subtype selectivity at dopaminergic and serotonergic receptors and those that possess dual mechanisms of action are being investigated. There has been tremendous progress over the past 50 years in understanding the role of monoamines in sexual function and the effect of pharmacologic agents which stimulate or antagonize monoaminergic receptors on sexual dysfunction. Nevertheless, large, double-blind, placebo-controlled studies evaluating the efficacy of currently available agents in populations without comorbid disorders are limited, preventing adequate interpretation of data. Continued research on sexual function and specific receptor subtypes will result in the development of more selective

Extrinsic factors regulate partial agonist efficacy of strychnine-sensitive glycine receptors

PubMed Central

Farroni, Jeffrey S; McCool, Brian A

2004-01-01

Background Strychnine-sensitive glycine receptors in many adult forebrain regions consist of alpha2 + beta heteromeric channels. This subunit composition is distinct from the alpha1 + beta channels found throughout the adult spinal cord. Unfortunately, the pharmacology of forebrain alpha2beta receptors are poorly defined compared to 'neonatal' alpha2 homomeric channels or 'spinal' alpha1beta heteromers. In addition, the pharmacologic properties of native alpha2beta glycine receptors have been generally distinct from receptors produced by heterologous expression. To identify subtype-specific pharmacologic tools for the forebrain alpha2beta receptors, it is important to identify a heterologous expression system that closely resembles these native glycine-gated chloride channels. Results While exploring pharmacological properties of alpha2beta glycine receptors compared to alpha2-homomers, we found that distinct heterologous expression systems appeared to differentially influence partial agonist pharmacology. The β-amino acid taurine possessed 30–50% efficacy for alpha2-containing receptor isoforms when expressed in HEK 293 cells. However, taurine efficacy was dramatically reduced in L-cell fibroblasts. Similar results were obtained for β-alanine. The efficacy of these partial agonists was also strongly reduced by the beta subunit. There were no significant differences in apparent strychnine affinity values calculated from concentration-response data between expression systems or subunit combinations. Nor did relative levels of expression correlate with partial agonist efficacy when compared within or between several different expression systems. Finally, disruption of the tubulin cytoskeleton reduced the efficacy of partial agonists in a subunit-dependent, but system-independent, fashion. Conclusions Our results suggest that different heterologous expression systems can dramatically influence the agonist pharmacology of strychnine-sensitive glycine receptors. In

Extrinsic factors regulate partial agonist efficacy of strychnine-sensitive glycine receptors.

PubMed

Farroni, Jeffrey S; McCool, Brian A

2004-08-09

Strychnine-sensitive glycine receptors in many adult forebrain regions consist of alpha2 + beta heteromeric channels. This subunit composition is distinct from the alpha1 + beta channels found throughout the adult spinal cord. Unfortunately, the pharmacology of forebrain alpha2beta receptors are poorly defined compared to 'neonatal' alpha2 homomeric channels or 'spinal' alpha1beta heteromers. In addition, the pharmacologic properties of native alpha2beta glycine receptors have been generally distinct from receptors produced by heterologous expression. To identify subtype-specific pharmacologic tools for the forebrain alpha2beta receptors, it is important to identify a heterologous expression system that closely resembles these native glycine-gated chloride channels. While exploring pharmacological properties of alpha2beta glycine receptors compared to alpha2-homomers, we found that distinct heterologous expression systems appeared to differentially influence partial agonist pharmacology. The beta-amino acid taurine possessed 30-50% efficacy for alpha2-containing receptor isoforms when expressed in HEK 293 cells. However, taurine efficacy was dramatically reduced in L-cell fibroblasts. Similar results were obtained for beta-alanine. The efficacy of these partial agonists was also strongly reduced by the beta subunit. There were no significant differences in apparent strychnine affinity values calculated from concentration-response data between expression systems or subunit combinations. Nor did relative levels of expression correlate with partial agonist efficacy when compared within or between several different expression systems. Finally, disruption of the tubulin cytoskeleton reduced the efficacy of partial agonists in a subunit-dependent, but system-independent, fashion. Our results suggest that different heterologous expression systems can dramatically influence the agonist pharmacology of strychnine-sensitive glycine receptors. In the systems examine here

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

Management of Depression in Patients with Dementia: Is Pharmacological Treatment Justified?

PubMed

Ford, Andrew H; Almeida, Osvaldo P

2017-02-01

Depression in the context of dementia is common and contributes to poorer outcomes in individuals and those who care for them. Non-pharmacological treatments are the preferred initial approach to managing these symptoms but data in support of these are scarce. There are a number of pharmacological treatment options available to clinicians but efficacy is uncertain and concern about potential side effects in an aging and vulnerable population needs to be taken into consideration. This review aims to provide a concise overview of pharmacological treatments for depression in dementia. Antidepressants are the mainstay of pharmacological treatment for clinically significant depression in the general population but evidence to support their use in dementia is mixed. Trials of antidepressants should generally be reserved for individuals with depression where the symptoms are distressing and surpass the threshold for major depression. Acetylcholinesterase inhibitors and memantine are effective in the symptomatic treatment of Alzheimer's disease but current evidence does not support their use to treat depressive symptoms in dementia. Similarly, antipsychotics and mood stabilizers have no proven efficacy for depression and the risk of adverse effects seems to outweigh any potential benefit. Pain can be a frequent problem in dementia and may have significant effects on behavior and mood. Preliminary evidence supports a role of adequate analgesia in improving mood in people with dementia.

An observational study of clozapine induced sedation and its pharmacological management.

PubMed

Ramos Perdigués, Sònia; Sauras Quecuti, Rosa; Mané, Anna; Mann, Louisa; Mundell, Clare; Fernandez-Egea, Emilio

2016-01-01

Clozapine induced sedation is common but its management is unclear. We analyzed the factors associated with clozapine-induced sedation and the efficacy of common pharmacological strategies. We conducted a naturalistic observational study using two years electronic records of a cohort patients and three analyses: a cross sectional analysis of factors associated with total number of hours slept (as an objective proxy of sedation), and two prospective analyses of which factors were associated with changes in hours slept and the efficacy of two pharmacological strategies. 133 patients were included, of which 64.7% slept at least 9h daily. Among monotherapy patients (n=30), only norclozapine levels (r=.367, p=.03) correlated with hours slept. Using the prospective cohort (n=107), 42 patients decreased the number of hours slept, due to decreasing clozapine (40%) or augmenting with aripiprazole (36%). These two strategies were recommended to 22 (20.6%) and 23 (21.5%) subjects respectively but the majority (81.8% and 73.9%) did not reduce number of hours slept. Thus, pharmacological and non-pharmacological factors are involved in sedation. Norclozapine plasma levels correlated with total sleeping hours. Reducing clozapine and aripiprazole augmentation were associated to amelioration of sedation, although both strategies were effective only in a limited numbers of subjects. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

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.

Local Anesthetics: Review of Pharmacological Considerations

PubMed Central

Becker, Daniel E; Reed, Kenneth L

2012-01-01

Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is so routine, and adverse effects are so infrequent, that providers may understandably overlook many of their pharmacotherapeutic principles. The purpose of this continuing education article is to provide a review and update of essential pharmacology for the various local anesthetic formulations in current use. Technical considerations will be addressed in a subsequent article. PMID:22822998

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.

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.

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

Lonicerae Japonicae Flos and Lonicerae Flos: A Systematic Pharmacology Review

PubMed Central

Li, Yujie; Cai, Weiyan; Weng, Xiaogang; Li, Qi; Wang, Yajie; Chen, Ying; Zhang, Wei; Yang, Qing; Guo, Yan; Zhu, Xiaoxin; Wang, Hainan

2015-01-01

Lonicerae japonicae flos, a widely used traditional Chinese medicine (TCM), has been used for several thousand years in China. Chinese Pharmacopeia once included Lonicerae japonicae flos of Caprifoliaceae family and plants of the same species named Lonicerae flos in general in the same group. Chinese Pharmacopeia (2005 Edition) lists Lonicerae japonicae flos and Lonicerae flos under different categories, although they have the similar history of efficacy. In this study, we research ancient books of TCM, 4 main databases of Chinese academic journals, and MEDLINE/PubMed to verify the origins and effects of Lonicerae japonicae flos and Lonicerae flos in traditional medicine and systematically summarized the research data in light of modern pharmacology and toxicology. Our results show that Lonicerae japonicae flos and Lonicerae flos are similar pharmacologically, but they also differ significantly in certain aspects. A comprehensive systematic review and a standard comparative pharmacological study of Lonicerae japonicae flos and Lonicerae flos as well as other species of Lonicerae flos support their clinical safety and application. Our study provides evidence supporting separate listing of Lonicerae japonicae flos and Lonicerae flos in Chinese Pharmacopeia as well as references for revision of relevant pharmacopeial records dealing with traditional efficacy of Lonicerae japonicae flos and Lonicerae flos. PMID:26257818

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.

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

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

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.

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.

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

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

The Efficacy and Clinical Safety of Various Analgesic Combinations for Post-Operative Pain after Third Molar Surgery: A Systematic Review and Meta-Analysis

PubMed Central

Au, Alvin Ho Yeung; Choi, Siu Wai; Cheung, Chi Wai; Leung, Yiu Yan

2015-01-01

Objectives To run a systematic review and meta-analysis of randomized clinical trials aiming to answer the clinical question “which analgesic combination and dosage is potentially the most effective and safe for acute post-operative pain control after third molar surgery?”. Materials and Methods A systematic search of computer databases and journals was performed. The search and the evaluations of articles were performed by 2 independent reviewers in 3 rounds. Randomized clinical trials related to analgesic combinations for acute post-operative pain control after lower third molar surgery that matched the selection criteria were evaluated to enter in the final review. Results Fourteen studies with 3521 subjects, with 10 groups (17 dosages) of analgesic combinations were included in the final review. The analgesic efficacy were presented by the objective pain measurements including sum of pain intensity at 6 hours (SPID6) and total pain relief at 6 hours (TOTPAR6). The SPID6 scores and TOTPAR6 scores of the reported analgesic combinations were ranged from 1.46 to 6.44 and 3.24 – 10.3, respectively. Ibuprofen 400mg with oxycodone HCL 5mg had superior efficacy (SPID6: 6.44, TOTPAR6: 9.31). Nausea was the most common adverse effect, with prevalence ranging from 0-55%. Ibuprofen 200mg with caffeine 100mg or 200mg had a reasonable analgesic effect with fewer side effects. Conclusion This systematic review and meta-analysis may help clinicians in their choices of prescribing an analgesic combination for acute post-operative pain control after lower third molar surgery. It was found in this systematic review Ibuprofen 400mg combined with oxycodone HCL 5mg has superior analgesic efficacy when compared to the other analgesic combinations included in this study. PMID:26053953

Efficacy of a comprehensive rehabilitation programme combined with pharmacological treatment in reducing pain in a group of OA patients on a waiting list for total joint replacement.

PubMed

Casale, Roberto; Damiani, Carlo; Rosati, Vanessa; Atzeni, Fabiola; Sarzi-Puttini, Piercarlo; Nica, Adriana S

2012-01-01

It has been shown that combined rehabilitation and pharmacological treatment reduce pain in subjects with osteoarthritis (OA), although the efficacy of either therapy alone may be limited. We studied the effects of a comprehensive rehabilitation programme alone and together with pharmacological treatment in relatively young OA patients awaiting total joint replacement (TJR). Forty-four OA patients randomly divided into two groups underwent three weeks of comprehensive day hospital rehabilitation treatment alone (group A) or in combination with acetaminophen 1g three times a day. Pain intensity was measured using a visual analogue scale (VAS) before and during treatment, and for four weeks afterwards, and compared between the groups using Student's t-test for unpaired data. In group A, pain intensity was not reduced after the first week of treatment (T0 vs. T1: p=0.739), but was significantly reduced from the end of the second week to the end of the observation period (p<0.01). In group B, pain intensity was significantly reduced (p<0.01) from the first week of treatment to the end of the observation period. The differences in the VAS score variations from T0 between the two groups were statistically significant throughout the study period (T0-T1: p=0.004, T0-T2: p=0.041, T0-T3: p=0.035, T0-T4: p=0.009, T0-T5: p=0.011, T0-T6: p=0.014 T0-T7: p=0.015). Rehabilitation is effective in reducing pain even in patients with severe OA on a waiting list for TJR, but its efficacy is boosted by adding appropriate pharmacological treatment.

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

Budget impact modeling for a single-tablet formulation of ibuprofen and famotidine for prevention of upper gastrointestinal ulcers in patients with osteoarthritis and/or rheumatoid arthritis.

PubMed

Kuan, Renee; Holt, Robert J; Johnson, Kenneth E; Kent, Jeffrey D; Peura, David A; Malone, Dan

2013-03-01

Single-tablet ibuprofen/famotidine is approved by the US Food and Drug Administration for the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis and to decrease the risk of developing upper gastrointestinal (GI) ulcers in patients taking ibuprofen for those indications. Currently, little is known about the cost impact of gastroprotective therapies, and an estimate of the financial consequences of adopting these therapies will be helpful to decision makers. The goal of this study was to review a model that evaluates the expected financial impact to US health care plans from the introduction of single-tablet ibuprofen/famotidine into the chronic NSAID user population. A budget impact model, considering a typical health plan of 1 million enrollees, was used to compare patients receiving: (1) single-tablet ibuprofen/famotidine; (2) chronic NSAID treatment plus any GI-protective agent; and (3) chronic NSAID treatment without a GI-protective agent. The expected medication cost for single-tablet ibuprofen/famotidine was $734,192 ($81,577 in year 1, $244,731 in year 2, and $407,884 in year 3), corresponding to a total per-member per-month cost of $0.020 ($0.007 in year 1, $0.020 in year 2, and $0.034 in year 3). Considering anticipated decreases in the use of other NSAIDs, the use of GI-protective agents, and GI complications, the total expected 3-year drug cost for single-tablet ibuprofen/famotidine was offset by 50%, representing an estimated total budget impact of $364,396 or $0.010 per member per month. Sensitivity analyses of cost and market share variables and clinical and drug characteristics identified the most influential variables to be the cost of the drug and persistence to the ibuprofen/famotidine formulation, respectively. The expected decrease in treatment costs for less serious GI-related complications illustrates the benefits of single-tablet ibuprofen/famotidine as a gastroprotective therapy in patients receiving chronic NSAID

The effects of a salicylate, ibuprofen, and naproxen on the disposition of methotrexate in patients with rheumatoid arthritis.

PubMed

Tracy, T S; Krohn, K; Jones, D R; Bradley, J D; Hall, S D; Brater, D C

1992-01-01

We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently treated with choline magnesium trisalicylate, ibuprofen, naproxen, or a non-NSAID analgesic (control treatment). The apparent systemic clearance of methotrexate was significantly reduced by all three treatments. Trisalicylate and ibuprofen both significantly reduced methotrexate renal clearance, but only the trisalicylate significantly displaced methotrexate from protein, increasing the fraction unbound by 28%. These data show that NSAIDs can affect the disposition of methotrexate, possibly increasing the potential for toxicity and necessitating dosage adjustments. However, large inter-subject variability precludes specific dosage recommendations.

Analgesic safety - myths, mysteries and misconceptions.

PubMed

Moore, R A

2015-05-01

Acute episodes of tension-type headache (TTH) are common and affect people of all ages, races and income levels. Two recommended and commonly used drugs for the treatment of this condition are ibuprofen and paracetamol. However, despite - or perhaps because of - their widespread use, many misconceptions persist about their comparative efficacy and safety. Are concerns about the gastrointenstinal (GI) safety of ibuprofen justified in the non-prescription over-the-counter (OTC) setting? Do low doses of ibuprofen - as used for TTH - increase the risk of heart attacks? Is the efficacy of ibuprofen and paracetamol really the same?

Pharmacology of P2X channels.

PubMed

Gever, Joel R; Cockayne, Debra A; Dillon, Michael P; Burnstock, Geoffrey; Ford, Anthony P D W

2006-08-01

Significant progress in understanding the pharmacological characteristics and physiological importance of homomeric and heteromeric P2X channels has been achieved in recent years. P2X channels, gated by ATP and most likely trimerically assembled from seven known P2X subunits, are present in a broad distribution of tissues and are thought to play an important role in a variety of physiological functions, including peripheral and central neuronal transmission, smooth muscle contraction, and inflammation. The known homomeric and heteromeric P2X channels can be distinguished from each other on the basis of pharmacological differences when expressed recombinantly in cell lines, but whether this pharmacological classification holds true in native cells and in vivo is less well-established. Nevertheless, several potent and selective P2X antagonists have been discovered in recent years and shown to be efficacious in various animal models including those for visceral organ function, chronic inflammatory and neuropathic pain, and inflammation. The recent advancement of drug candidates targeting P2X channels into human trials, confirms the medicinal exploitability of this novel target family and provides hope that safe and effective medicines for the treatment of disorders involving P2X channels may be identified in the near future.

Operational models of pharmacological agonism.

PubMed

Black, J W; Leff, P

1983-12-22

The traditional receptor-stimulus model of agonism began with a description of drug action based on the law of mass action and has developed by a series of modifications, each accounting for new experimental evidence. By contrast, in this paper an approach to modelling agonism is taken that begins with the observation that experimental agonist-concentration effect, E/[A], curves are commonly hyperbolic and develops using the deduction that the relation between occupancy and effect must be hyperbolic if the law of mass action applies at the agonist-receptor level. The result is a general model that explicitly describes agonism by three parameters: an agonist-receptor dissociation constant, KA; the total receptor concentration, [R0]; and a parameter, KE, defining the transduction of agonist-receptor complex, AR, into pharmacological effect. The ratio, [R0]/KE, described here as the 'transducer ratio', tau, is a logical definition for the efficacy of an agonist in a system. The model may be extended to account for non-hyperbolic E/[A] curves with no loss of meaning. Analysis shows that an explicit formulation of the traditional receptor-stimulus model is one particular form of the general model but that it is not the simplest. An alternative model is proposed, representing the cognitive and transducer functions of a receptor, that describes agonist action with one fewer parameter than the traditional model. In addition, this model provides a chemical definition of intrinsic efficacy making this parameter experimentally accessible in principle. The alternative models are compared and contrasted with regard to their practical and conceptual utilities in experimental pharmacology.

Differential protein modulation by ketoprofen and ibuprofen underlines different cellular response by gastric epithelium.

PubMed

Brandolini, Laura; d'Angelo, Michele; Antonosante, Andrea; Villa, Sara; Cristiano, Loredana; Castelli, Vanessa; Benedetti, Elisabetta; Catanesi, Mariano; Aramini, Andrea; Luini, Alberto; Parashuraman, Seetharaman; Mayo, Emilia; Giordano, Antonio; Cimini, Annamaria; Allegretti, Marcello

2018-03-01

Ketoprofen L-lysine salt (KLS), is widely used due to its analgesic efficacy and tolerability, and L-lysine was reported to increase the solubility and the gastric tolerance of ketoprofen. In a recent report, L-lysine salification has been shown to exert a gastroprotective effect due to its specific ability to counteract the NSAIDs-induced oxidative stress and up-regulate gastroprotective proteins. In order to derive further insights into the safety and efficacy profile of KLS, in this study we additionally compared the effect of lysine and arginine, another amino acid counterion commonly used for NSAIDs salification, in control and in ethanol challenged human gastric mucosa model. KLS is widely used for the control of post-surgical pain and for the management of pain and fever in inflammatory conditions in children and adults. It is generally well tolerated in pediatric patients, and data from three studies in >900 children indicate that oral administration is well tolerated when administered for up to 3 weeks after surgery. Since only few studies have so far investigated the effect of ketoprofen on gastric mucosa maintenance and adaptive mechanisms, in the second part of the study we applied the cMap approach to compare ketoprofen-induced and ibuprofen-induced gene expression profiles in order to explore compound-specific targeted biological pathways. Among the several genes exclusively modulated by ketoprofen, our attention was particularly focused on genes involved in the maintenance of gastric mucosa barrier integrity (cell junctions, morphology, and viability). The hypothesis was further validated by Real-time PCR. © 2017 Wiley Periodicals, Inc.

From prescription-only (Rx) to over-the-counter (OTC) status in Germany 2006-2015: pharmacological perspectives on regulatory decisions.

PubMed

Barrenberg, Eva; Garbe, Edeltraut

2017-07-01

Little is known about the extent of switches from prescription-only (Rx) to over-the-counter (OTC) status in Europe and about the pharmacological properties of the switched substances. The objectives of this study were to provide an overview of the substances that were switched from Rx to OTC status in Germany between 2006 and 2015 and to assess their pharmacological properties. Session minutes of the German Expert Advisory Committee for Prescription-Only Issues, changes to the German Ordinance on Prescription-Only Medicines and the Summary of Product Characteristics of the switched substances were analysed. Pharmacological properties were studied in relation to the EU Guideline on Changing the Classification for the Supply of a Medicinal Product for Human Use (the 'EU switch guide'). Between 2006 and 2015, seven substances (almotriptan, omeprazole, benzydamine, ibuprofen/pseudoephedrine, racecadotril, ketotifen and levonorgestrel) were switched from Rx to OTC status in Germany. In all cases, the OTC status was restricted to certain indications, doses, pack sizes, or other limitations. Notwithstanding recommendations of the EU switch guide, some of the switched substances might interact with commonly used drugs potentially resulting in serious adverse drug reactions or have contraindications or warnings regarding substantial parts of the population. The stipulations of the EU switch guide were fully met for only some switches, while this was not completely the case for others. Further development of guidance on balancing risks and benefits of OTC availability is recommended.

Future pharmacological treatments for substance use disorders

PubMed Central

Forray, Ariadna; Sofuoglu, Mehmet

2014-01-01

Substance use disorders represent a serious public health and social issue worldwide. Recent advances in our understanding of the neurobiological basis of the addictive processes have led to the development of a growing number of pharmacological agents to treat addictions. Despite this progress, there are no approved pharmacological treatments for cocaine, methamphetamine and cannabis addiction. Moving treatment development to the next stage will require novel ways of approaching substance use disorders. One such novel approach is to target individual vulnerabilities, such as cognitive function, sex differences and psychiatric comorbidities. This review provides a summary of promising pharmacotherapies for alcohol, opiate, stimulant and nicotine addictions. Many medications that target positive and negative reinforcement of drugs, as well as individual vulnerabilities to addiction, are in different phases of development. Clinical trials testing the efficacy of these medications for substance use disorder are warranted. PMID:23039267

Fraxinus: A Plant with Versatile Pharmacological and Biological Activities.

PubMed

Sarfraz, Iqra; Rasul, Azhar; Jabeen, Farhat; Younis, Tahira; Zahoor, Muhammad Kashif; Arshad, Muhammad; Ali, Muhammad

2017-01-01

Fraxinus , a member of the Oleaceae family, commonly known as ash tree is found in northeast Asia, north America, east and western France, China, northern areas of Pakistan, India, and Afghanistan. Chemical constituents of Fraxinus plant include various secoiridoids, phenylethanoids, flavonoids, coumarins, and lignans; therefore, it is considered as a plant with versatile biological and pharmacological activities. Its tremendous range of pharmacotherapeutic properties has been well documented including anticancer, anti-inflammatory, antioxidant, antimicrobial, and neuroprotective. In addition, its bioactive phytochemicals and secondary metabolites can be effectively used in cosmetic industry and as a competent antiaging agent. Fraxinus presents pharmacological effectiveness by targeting the novel targets in several pathological conditions, which provide a spacious therapeutic time window. Our aim is to update the scientific research community with recent endeavors with specifically highlighting the mechanism of action in different diseases. This potentially efficacious pharmacological drug candidate should be used for new drug discovery in future. This review suggests that this plant has extremely important medicinal utilization but further supporting studies and scientific experimentations are mandatory to determine its specific intracellular targets and site of action to completely figure out its pharmacological applications.

Fraxinus: A Plant with Versatile Pharmacological and Biological Activities

PubMed Central

Sarfraz, Iqra; Jabeen, Farhat; Younis, Tahira; Arshad, Muhammad; Ali, Muhammad

2017-01-01

Fraxinus, a member of the Oleaceae family, commonly known as ash tree is found in northeast Asia, north America, east and western France, China, northern areas of Pakistan, India, and Afghanistan. Chemical constituents of Fraxinus plant include various secoiridoids, phenylethanoids, flavonoids, coumarins, and lignans; therefore, it is considered as a plant with versatile biological and pharmacological activities. Its tremendous range of pharmacotherapeutic properties has been well documented including anticancer, anti-inflammatory, antioxidant, antimicrobial, and neuroprotective. In addition, its bioactive phytochemicals and secondary metabolites can be effectively used in cosmetic industry and as a competent antiaging agent. Fraxinus presents pharmacological effectiveness by targeting the novel targets in several pathological conditions, which provide a spacious therapeutic time window. Our aim is to update the scientific research community with recent endeavors with specifically highlighting the mechanism of action in different diseases. This potentially efficacious pharmacological drug candidate should be used for new drug discovery in future. This review suggests that this plant has extremely important medicinal utilization but further supporting studies and scientific experimentations are mandatory to determine its specific intracellular targets and site of action to completely figure out its pharmacological applications. PMID:29279716

UV Spectrophotometric Simultaneous Determination of Paracetamol and Ibuprofen in Combined Tablets by Derivative and Wavelet Transforms

PubMed Central

Hoang, Vu Dang; Ly, Dong Thi Ha; Tho, Nguyen Huu; Minh Thi Nguyen, Hue

2014-01-01

The application of first-order derivative and wavelet transforms to UV spectra and ratio spectra was proposed for the simultaneous determination of ibuprofen and paracetamol in their combined tablets. A new hybrid approach on the combined use of first-order derivative and wavelet transforms to spectra was also discussed. In this application, DWT (sym6 and haar), CWT (mexh), and FWT were optimized to give the highest spectral recoveries. Calibration graphs in the linear concentration ranges of ibuprofen (12–32 mg/L) and paracetamol (20–40 mg/L) were obtained by measuring the amplitudes of the transformed signals. Our proposed spectrophotometric methods were statistically compared to HPLC in terms of precision and accuracy. PMID:24949492

UV spectrophotometric simultaneous determination of paracetamol and ibuprofen in combined tablets by derivative and wavelet transforms.

PubMed

Hoang, Vu Dang; Ly, Dong Thi Ha; Tho, Nguyen Huu; Nguyen, Hue Minh Thi

2014-01-01

The application of first-order derivative and wavelet transforms to UV spectra and ratio spectra was proposed for the simultaneous determination of ibuprofen and paracetamol in their combined tablets. A new hybrid approach on the combined use of first-order derivative and wavelet transforms to spectra was also discussed. In this application, DWT (sym6 and haar), CWT (mexh), and FWT were optimized to give the highest spectral recoveries. Calibration graphs in the linear concentration ranges of ibuprofen (12-32 mg/L) and paracetamol (20-40 mg/L) were obtained by measuring the amplitudes of the transformed signals. Our proposed spectrophotometric methods were statistically compared to HPLC in terms of precision and accuracy.

Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria

PubMed Central

Rivera-Leyva, J. C.; García-Flores, M.; Valladares-Méndez, A.; Orozco-Castellanos, L. M.; Martínez-Alfaro, M.

2012-01-01

In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386

Metabolite profiling of carbamazepine and ibuprofen in Solea senegalensis bile using high-resolution mass spectrometry.

PubMed

Aceña, Jaume; Pérez, Sandra; Eichhorn, Peter; Solé, Montserrat; Barceló, Damià

2017-09-01

The widespread occurrence of pharmaceuticals in the aquatic environment has raised concerns about potential adverse effects on exposed wildlife. Very little is currently known on exposure levels and clearance mechanisms of drugs in marine fish. Within this context, our research was focused on the identification of main metabolic reactions, generated metabolites, and caused effects after exposure of fish to carbamazepine (CBZ) and ibuprofen (IBU). To this end, juveniles of Solea senegalensis acclimated to two temperature regimes of 15 and 20 °C for 60 days received a single intraperitoneal dose of these drugs. A control group was administered the vehicle (sunflower oil). Bile samples were analyzed by ultra-high-performance liquid chromatography-high-resolution mass spectrometry on a Q Exactive (Orbitrap) system, allowing to propose plausible identities for 11 metabolites of CBZ and 13 metabolites of IBU in fish bile. In case of CBZ metabolites originated from aromatic and benzylic hydroxylation, epoxidation, and ensuing O-glucuronidation, O-methylation of a catechol-like metabolite was also postulated. Ibuprofen, in turn, formed multiple hydroxyl metabolites, O-glucuronides, and (hydroxyl)-acyl glucuronides, in addition to several taurine conjugates. Enzymatic responses after drug exposures revealed a water temperature-dependent induction of microsomal carboxylesterases. The metabolite profiling in fish bile provides an important tool for pharmaceutical exposure assessment. Graphical abstract Studies of metabolism of carbamazepine and ibuprofen in fish.

Assessing the impact of diclofenac, ibuprofen and sildenafil citrate (Viagra®) on the fertilisation biology of broadcast spawning marine invertebrates.

PubMed

Mohd Zanuri, Norlaila Binti; Bentley, Matthew G; Caldwell, Gary S

2017-06-01

Exposure to synthetic chemicals is a key environmental challenge faced by aquatic organisms. The time and dose effects of the pharmaceuticals diclofenac, ibuprofen, and sildenafil citrate on sperm motility and successful fertilisation are studied using the echinoderms, Asterias rubens and Psammechinus miliaris, and the polychaete worm Arenicola marina, all important components of the marine benthos. Motility was reduced for all species when exposed to diclofenac concentrations ≥0.1 μg/L. Exposure to ≥1.0 μg/L of ibuprofen affected only P. miliaris gametes and fertilisation success of A. marina. A. rubens and P. miliaris sperm increased in both percentage motility and swimming velocity when exposed to sildenafil citrate at concentrations ≥18 and ≥ 50 ng/L, respectively. Pre-incubation of sperm with sildenafil citrate significantly increased fertilisation success in A. rubens and P. miliaris but not in A. marina. Pre-incubated A. rubens oocytes fertilised successfully in ibuprofen. According to EU Directive 93/67/EEC, diclofenac is classified as a very toxic substance to gametes of A. rubens, P. miliaris, and A. marina (EC 50  = 100-1000 μg/L) while ibuprofen is classified as very toxic to gametes of P. miliaris but non-toxic to gametes of A. marina (EC 50  > 10,000 μg/L). The present study indicates that diclofenac exposure may have negative impacts on invertebrate reproductive success, whereas ibuprofen potentially may compromise P. miliaris reproduction. This study provides a valuable insight into the mechanisms that allow marine invertebrates to survive and reproduce in contaminated and changing habitats. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular Dynamics Simulation Study of the Selectivity of a Silica Polymer for Ibuprofen

PubMed Central

Concu, Riccardo; Cordeiro, M. Natalia D. S.

2016-01-01

In the past few years, the sol-gel polycondensation technique has been increasingly employed with great success as an alternative approach to the preparation of molecularly imprinted materials (MIMs). The main aim of this study was to study, through a series of molecular dynamics (MD) simulations, the selectivity of an imprinted silica xerogel towards a new template—the (±)-2-(P-Isobutylphenyl) propionic acid (Ibuprofen, IBU). We have previously demonstrated the affinity of this silica xerogel toward a similar molecule. In the present study, we simulated the imprinting process occurring in a sol-gel mixture using the Optimized Potentials for Liquid Simulations-All Atom (OPLS-AA) force field, in order to evaluate the selectivity of this xerogel for a template molecule. In addition, for the first time, we have developed and verified a new parameterisation for the Ibuprofen® based on the OPLS-AA framework. To evaluate the selectivity of the polymer, we have employed both the radial distribution functions, interaction energies and cluster analyses. PMID:27399685

Molecular Dynamics Simulation Study of the Selectivity of a Silica Polymer for Ibuprofen.

PubMed

Concu, Riccardo; Cordeiro, M Natalia D S

2016-07-07

In the past few years, the sol-gel polycondensation technique has been increasingly employed with great success as an alternative approach to the preparation of molecularly imprinted materials (MIMs). The main aim of this study was to study, through a series of molecular dynamics (MD) simulations, the selectivity of an imprinted silica xerogel towards a new template-the (±)-2-(P-Isobutylphenyl) propionic acid (Ibuprofen, IBU). We have previously demonstrated the affinity of this silica xerogel toward a similar molecule. In the present study, we simulated the imprinting process occurring in a sol-gel mixture using the Optimized Potentials for Liquid Simulations-All Atom (OPLS-AA) force field, in order to evaluate the selectivity of this xerogel for a template molecule. In addition, for the first time, we have developed and verified a new parameterisation for the Ibuprofen(®) based on the OPLS-AA framework. To evaluate the selectivity of the polymer, we have employed both the radial distribution functions, interaction energies and cluster analyses.

Guaifenesin enhances the analgesic potency of ibuprofen, nimesulide and celecoxib in mice.

PubMed

Sliva, Jiri; Dolezal, Tomas; Sykora, David; Vosmanska, Magda; Krsiak, Miloslav

2009-01-01

Previously, we found that guaifenesin enhances analgesia induced by paracetamol. The aim of the present study was to determine whether guaifenesin is able to also increase analgesic activity in the non-steroid anti-inflammatory drugs ibuprofen, nimesulide and celecoxib. In addition we investigated the influence of guaifenesin on plasma levels of nimesulide. A model of visceral pain consisting of intraperitoneal injection of acetic acid (writhing test) was used. Levels of nimesulide in plasma were measured by HPLC. All drugs were given orally and tested in mice. Guaifenesin alone did not produce any antinociceptive effect. Simultaneous administration of guaifenesin (200 mg/kg) and subanalgesic doses of ibuprofen (10 and 30 mg/kg), nimesulide (10 and 20 mg/kg) or celecoxib (1 and 5 mg/kg) resulted in a significant antinociceptive effects. The plasma levels of nimesulide were significantly higher in combination with guaifenesin at 30, 60 and 90 min after oral administration in comparison to nimesulide monotherapy. The present results suggest that guaifenesin might enhance the analgesic activity of various non-steroidal anti-inflammatory drugs.

Pharmacologic treatment of alcoholism.

PubMed

Anton, Raymond F; Schacht, Joseph P; Book, Sarah W

2014-01-01

Progress in understanding the neuroscience of addiction has significantly advanced the development of more efficacious medications for the treatment of alcohol use disorders (AUD). While several medications have been approved by regulatory bodies around the world for the treatment of AUD, they are not universally efficacious. Recent research has yielded improved understanding of the genetics and brain circuits that underlie alcohol reward and its habitual use. This research has contributed to pharmacogenetic studies of medication response, and will ultimately lead to a more "personalized medicine" approach to AUD pharmacotherapy. This chapter summarizes work on clinically available medications (both approved by regulatory bodies and investigational) for the treatment of alcohol dependence, as well as the psychiatric disorders that are commonly comorbid with AUD. Studies that have evaluated genetic influences on medication response and those that have employed neuroimaging to probe mechanisms of medication action or response are highlighted. Finally, new targets discovered in animal models for possible pharmacologic intervention in humans are overviewed and future directions in medications development provided. © 2014 Elsevier B.V. All rights reserved.

Cognitive-Behavioral and Pharmacologic Interventions for Children's Distress during Painful Medical Procedures.

ERIC Educational Resources Information Center

Jay, Susan M.; And Others

1987-01-01

Evaluated efficacy of cognitive-behavioral intervention package and low-risk pharmacologic intervention (oral Valium) as compared with minimal treatment-attention control condition, in reducing children leukemia patients' distress during bone marrow aspirations. The cognitive-behavioral therapy reduced behavioral distress, pain ratings and pulse…

Influence of CYP2C8 polymorphisms on the hydroxylation metabolism of paclitaxel, repaglinide and ibuprofen enantiomers in vitro.

PubMed

Yu, Lushan; Shi, Da; Ma, Liping; Zhou, Quan; Zeng, Su

2013-07-01

CYP2C8 plays an important role in the metabolism of various drugs, such as paclitaxel, repaglinide and ibuprofen. Polymorphisms in the CYP2C8 gene were shown to influence interindividual differences in the pharmacokinetics of paclitaxel, repaglinide and ibuprofen enantiomers. In this study, three CYP2C8 allelic variants (CYP2C8.2, CYP2C8.3 and CYP2C8.4) and wild-type CYP2C8 (CYP2C8.1) were co-expressed for the first time with human cytochrome P450 oxidoreductase (POR) and cytochrome b5 by using a baculovirus-assisted insect cell expression system. Further, the effects of genotype-phenotype correlations of CYP2C8 alleles on the metabolism of paclitaxel, repaglinide and ibuprofen enantiomers were evaluated. The CLint values of CYP2C8.2, CYP2C8.3 and CYP2C8.4 for paclitaxel were 47.7%, 64.3% and 30.2% of that of CYP2C8.1 (p<0.01). The CLint values of CYP2C8.2 and CYP2C8.4 for repaglinide were 77.9% and 80.2% of that of CYP2C8.1 (p<0.05), respectively, while the CLint value of CYP2C8.3 was 1.31-fold higher than that of CYP2C8.1 (p<0.05). The relative CLint values of CYP2C8.2, CYP2C8.3 and CYP2C8.4 were 110.5%, 72.3% and 49.7% of that of CYP2C8.1 and were 124.6%, 83.4% and 47.4% of that of CYP2C8.1 for R-ibuprofen and S-ibuprofen, respectively. Comparing hydroxylation by CYP2C8.1 and CYP2C8.3 resulted in higher and lower intrinsic clearance of repaglinide and ibuprofen enantiomers, respectively. These in vitro findings were consistent with the pharmacokinetics in volunteers who were heterozygous or homozygous carriers of CYP2C8*3. The results of this study provide useful information for predicting CYP2C8 phenotypes and may contribute to individualized drug therapy in the future. Copyright © 2013 John Wiley & Sons, Ltd.

Application of guar gum biopolymer in the prescription of tablets with sodium ibuprofen--quality tests and pharmaceutical availability in vitro.

PubMed

Berner-Strzelczyk, Aneta; Kołodziejska, Justyna; Zgoda, Marian Mikołaj

2006-01-01

The increasing interest of the technology of drug form in natural biopolymers has become the reason for undertaking investigations on the possibility of guar gum application in the prescription of oral solid form of a drug. Alternative compositions and technology of the production of tablets of regulated in time sodium ibuprofen release were worked out for children. Two series of tablets were prepared with guar gum (5 and 10% content) and a series without the biopolymer. The tablet mass in each case contained keryostatic sorbitol and bioadhesive polyvinylpyrrolidone. All tablets were tested as regards the quality of production, compliance with the requirements of Polish Pharmacopoeia VI and potential therapeutic usefulness, manifestation of which is pharmaceutical availability of the therapeutic agent (sodium ibuprofen). The tests demonstrated that the produced tablets with sodium ibuprofen have proper physicochemical properties, in compliance with Polish Pharmacopoeia VI requirements. Application of biopolymer of guar gum type as adjuvant substance contributes to the improvement of the tablet hardness parameters and prevents technological problems (lining mixture of powders to tableting machine punch). The designed tablets demonstrate proper pharmaceutical availability of over 80%. Introduction of guar gum into their prescription prolonged their disintegration time and the rate of sodium ibuprofen release, which predisposes the produced form of a drug to have the function of a tablet with slowed-down release.

Pharmacological approaches to the treatment of complicated grief: rationale and a brief review of the literature

PubMed Central

Bui, Eric; Nadal-Vicens, Mireya; M. Simon, Naomi

2012-01-01

Complicated grief (CG) is a common and often under-acknowledged cause of profound impairment experienced after the loss of a loved one. Although both clinical and basic research suggests that pharmacological agents might be of use in the treatment of CG, research on pharmacological approaches to this condition is still scarce. Three open-label trials and one randomized trial on bereavement-related depression suggest that tricyclic antidepressants may be effective, although they may be more efficacious for depressive symptoms than for grief-specific symptoms. Four open-label trials (total number of participants, 50) of selective serotonin reuptake inhibitors (SSRIs) have yielded results, providing very preliminary support that they might be effective in the treatment of CG, both as a standalone treatment and in conjunction with psychotherapeutic interventions. These more recent studies have shown an effect on both depression and grief-specific scales. Furthermore, therapeutic interventions for CG may be more effective in conjunction with SSRI administration. Given the small number of pharmacological studies to date, there is a need for randomized trials to test the potential efficacy of pharmacological agents in the treatment of CG. PMID:22754287

Efficacy of Various Analgesics on Shoulder Function and Rotator Cuff Tendon-to-Bone Healing in a Rat (Rattus norvegicus) Model

PubMed Central

Caro, Adam C; Tucker, Jennica J; Yannascoli, Sarah M; Dunkman, Andrew A; Thomas, Stephen J; Soslowsky, Louis J

2014-01-01

Although relief of postoperative pain is an imperative aspect of animal welfare, analgesics that do not interfere with the scientific goals of the study must be used. Here we compared the efficacy of different analgesic agents by using an established rat model of supraspinatus tendon healing and a novel gait-analysis system. We hypothesized that different analgesic agents would all provide pain relief in this model but would cause differences in tendon-to-bone healing and gait parameters. Buprenorphine, ibuprofen, tramadol–gabapentin, and acetaminophen were compared with a no-analgesia control group. Gait measures (stride length and vertical force) on the operative forelimb differed between the control group and both the buprenorphine (2 and 4 d postsurgery) and ibuprofen (2 d postsurgery) groups. Step length was different in the control group as compared with the tramadol–gabapentin (2 d after surgery), buprenorphine (2 and 4 d after surgery), and ibuprofen (2 d after surgery) groups. Regarding tendon-to-bone healing, the ibuprofen group showed less stiffness at the insertion site; no other differences in tendon-to-bone healing were detected. In summary, the analgesics evaluated were associated with differences in both animal gait and tendon-to-bone healing. This information will be useful for improving the management of postsurgical pain without adversely affecting tissue healing. Given its ability to improve gait without impeding healing, we recommend use of buprenorphine for postsurgical pain management in rats. In addition, our gait-analysis system can be used to evaluate new analgesics. PMID:24602546

Sarcopenia: pharmacology of today and tomorrow.

PubMed

Brotto, Marco; Abreu, Eduardo L

2012-12-01

Sarcopenia remains largely undiagnosed and undertreated because of the lack of a universally accepted definition, effective ways to measure it, and identification of the outcomes that should guide treatment efficacy. An ever-growing number of clinicians and researchers along with funding and regulatory agencies have gradually recognized that sarcopenia is a human condition that requires both prevention and treatment. In this article, we review sarcopenia and its common and less known pharmacological treatments, attempt to define sarcopenia in its broader context, and present some new ideas for potential future treatment for this devastating condition.

Investigation of surfactant/cosurfactant synergism impact on ibuprofen solubilization capacity and drug release characteristics of nonionic microemulsions.

PubMed

Djekic, Ljiljana; Primorac, Marija; Filipic, Slavica; Agbaba, Danica

2012-08-20

The current study investigates the performances of the multicomponent mixtures of nonionic surfactants regarding the microemulsion stabilisation, drug solubilization and in vitro drug release kinetic. The primary surfactant was PEG-8 caprylic/capric glycerides (Labrasol). The cosurfactants were commercially available mixtures of octoxynol-12 and polysorbate 20 without or with the addition of PEG-40 hydrogenated castor oil (Solubilisant gamma 2421 and Solubilisant gamma 2429, respectively). The oil phase of microemulsions was isopropyl myristate. Phase behaviour study of the pseudo-ternary systems Labrasol/cosurfactant/oil/water at surfactant-to-cosurfactant weight ratios (K(m)) 40:60, 50:50 and 60:40, revealed a strong synergism in the investigated tensides mixtures for stabilisation of microemulsions containing up to 80% (w/w) of water phase at surfactant +cosurfactant-to-oil weight ratio (SCoS/O) 90:10. Solubilization of a model drug ibuprofen in concentration common for topical application (5%, w/w) was achieved at the water contents below 50% (w/w). Drug free and ibuprofen-loaded microemulsions M1-M6, containing 45% (w/w) of water phase, were prepared and characterized by polarized light microscopy, conductivity, pH, rheological and droplet size measurements. In vitro ibuprofen release kinetics from the microemulsions was investigated using paddle-over-enhancer cell method and compared with the commercial 5% (w/w) ibuprofen hydrogel product (Deep Relief, Mentholatum Company Ltd., USA). The investigated microemulsions were isotropic, low viscous Bingham-type liquids with the pH value (4.70-6.61) suitable for topical application. The different efficiency of the tensides mixtures for microemulsion stabilisation was observed, depending on the cosurfactant type and K(m) value. Solubilisant gamma 2429 as well as higher K(m) (i.e., lower relative content of the cosurfactant) provided higher surfactant/cosurfactant synergism. The drug molecules were predominantly

Condensed bridgehead nitrogen heterocyclic system: synthesis and pharmacological activities of 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole derivatives of ibuprofen and biphenyl-4-yloxy acetic acid.

PubMed

Amir, Mohd; Kumar, Harish; Javed, S A

2008-10-01

Several 3,6-disubstituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazoles were prepared by condensation of 4-amino-5-substituted-3-mercapto-(4H)-1,2,4-triazoles (3a,b) with various substituted aromatic acids and aryl/alkyl isothiocyanates through a one-pot reaction. These compounds were investigated for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, antibacterial and antifungal activities. Some of the synthesized compounds showed potent anti-inflammatory activity along with minimal ulcerogenic effect and lipid peroxidation, compared to those of ibuprofen and flurbiprofen. Some of the tested compounds also showed moderate antimicrobial activity against tested bacterial and fungal strains.

Current Pharmacological Approaches to Reduce Chorea in Huntington's Disease.

PubMed

Coppen, Emma M; Roos, Raymund A C

2017-01-01

There are currently no effective pharmacological agents available to stop or prevent the progression of Huntington's disease (HD), a rare hereditary neurodegenerative disorder. In addition to psychiatric symptoms and cognitive impairments, HD causes progressive motor disturbances, in particular choreiform movements, which are characterized by unwanted contractions of the facial muscles, trunk and extremities. Management of choreiform movements is usually advised if chorea interferes with daily functioning, causes social isolation, gait instability, falls, or physical injury. Although drugs to reduce chorea are available, only few randomized controlled studies have assessed the efficacy of these drugs, resulting in a high variety of prescribed drugs in clinical practice. The current pharmacological treatment options to reduce chorea in HD are outlined in this review, including the latest results on deutetrabenazine, a newly developed pharmacological agent similar to tetrabenazine, but with suggested less peak dose side effects. A review of the existing literature was conducted using the PubMed, Cochrane and Medline databases. In conclusion, mainly tetrabenazine, tiapride (in European countries), olanzapine, and risperidone are the preferred first choice drugs to reduce chorea among HD experts. In the existing literature, these drugs also show a beneficial effect on motor symptom severity and improvement of psychiatric symptoms. Generally, it is recommended to start with a low dose and increase the dose with close monitoring of any adverse effects. New interesting agents, such as deutetrabenazine and pridopidine, are currently under development and more randomized controlled trials are warranted to assess the efficacy on chorea severity in HD.

Determination of ibuprofen enantiomers in breast milk using vortex-assisted matrix solid-phase dispersion and direct chiral liquid chromatography.

PubMed

León-González, M E; Rosales-Conrado, N

2017-09-08

A mixture of β-cyclodextrin (β-CD) and primary and secondary amine (PSA) sorbents was employed for the extraction and quantification of ibuprofen enantiomers from human breast milk, combining a vortex-assisted matrix solid-phase dispersion method (MSPD) and direct chiral liquid chromatography (CLC) with ultraviolet detection (UV). The MSPD sample preparation procedure was optimized focusing on both the type and amount of dispersion/sorption sorbents and the nature of the elution solvent, in order to obtain acceptable recoveries and avoiding enantiomer conversion. These MSPD parameters were optimized with the aid of an experimental design approach. Hence, a factorial design was used for identification of the main variables affecting the extraction process of ibuprofen enantiomers. Under optimum selected conditions, MSPD combined with direct CLC-UV was successfully applied for ibuprofen enantiomeric determination in breast milk at enantiomer levels between 0.15 and 6.0μgg -1 . The proposed analytical method also provided good repeatability, with relative standard deviations of 6.4% and 8.3% for the intra-day and inter-day precision, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Membrane penetration enhancement of ibuprofen using supersaturation.

PubMed

Iervolino, M; Raghavan, S L; Hadgraft, J

2000-04-05

Permeation enhancement of ibuprofen from supersaturated solutions formed using the cosolvent technique was investigated using silicone as a model membrane. Hydroxpropyl methyl cellulose and hydroxpropyl-beta-cyclodextrin were used to stabilise the supersaturated states. Physical stability studies showed best results for low drug concentrations in a 40:60 propylene glycol/water cosolvent system. Variations in flux across model silicone membranes from saturated solutions were observed as the PG content was increased. The flux of IBU increased with the degree of saturation for solutions prepared in a 40:60 PG/water cosolvent mixture. HPMC and CD were found to be effective in enhancing the stability of supersaturated solutions of IBU. The mechanisms of action are different for the two additives and are discussed.

The protein binding substance Ibuprofen does not affect the T1 time or partition coefficient in contrast-enhanced cardiovascular magnetic resonance

PubMed Central

2012-01-01

Background Contrast enhanced cardiovascular magnetic resonance (CMR) with T1 mapping enables quantification of diffuse myocardial fibrosis. Various factors, however, can interfere with T1 measurements. The purpose of the current study was to assess the effect of co-medication with a typical protein binding drug (Ibuprofen) on T1 values in vitro and in vivo. Methods 50 vials were prepared with different concentrations of gadobenate dimeglumine, Ibuprofen and human serum albumin in physiologic NaCl solution and imaged at 1.5T with a spin echo sequence at multiple TRs to measure T1 values and calculate relaxivities. 10 volunteers (5 men; 31±6.3 years) were imaged at 1.5T. T1 values for myocardium and blood pool were determined for various time points after administration of 0.15mmol/kg gadobenate dimeglumine using a modified look-locker inversion-recovery sequence before and after administration of Ibuprofen over 24 hours. The partition coefficient was calculated as ΔR1myocardium/ΔR1blood, where R1=1/T1. Results In vitro no significant correlation was found between relaxivity and Ibuprofen concentration, neither in absence (r=−0.15, p=0.40) nor in presence of albumin (r=−0.32, p=0.30). In vivo there was no significant difference in post contrast T1 times of myocardium and blood, respectively and also in the partition coefficient between exam 1 and 2 (p>0.05). There was good agreement of the T1 times of myocardium and blood and the partition coefficient, respectively between exam 1 and 2. Conclusions Contrast enhanced T1 mapping is unaffected by co-medication with the protein binding substance Ibuprofen and has an excellent reproducibility. PMID:23067266

Molecular Pharmacology of δ-Opioid Receptors

PubMed Central

Gendron, Louis; Cahill, Catherine M.; von Zastrow, Mark; Schiller, Peter W.

2016-01-01

Opioids are among the most effective analgesics available and are the first choice in the treatment of acute severe pain. However, partial efficacy, a tendency to produce tolerance, and a host of ill-tolerated side effects make clinically available opioids less effective in the management of chronic pain syndromes. Given that most therapeutic opioids produce their actions via µ-opioid receptors (MOPrs), other targets are constantly being explored, among which δ-opioid receptors (DOPrs) are being increasingly considered as promising alternatives. This review addresses DOPrs from the perspective of cellular and molecular determinants of their pharmacological diversity. Thus, DOPr ligands are examined in terms of structural and functional variety, DOPrs’ capacity to engage a multiplicity of canonical and noncanonical G protein–dependent responses is surveyed, and evidence supporting ligand-specific signaling and regulation is analyzed. Pharmacological DOPr subtypes are examined in light of the ability of DOPr to organize into multimeric arrays and to adopt multiple active conformations as well as differences in ligand kinetics. Current knowledge on DOPr targeting to the membrane is examined as a means of understanding how these receptors are especially active in chronic pain management. Insight into cellular and molecular mechanisms of pharmacological diversity should guide the rational design of more effective, longer-lasting, and better-tolerated opioid analgesics for chronic pain management. PMID:27343248

Introduction of β-cyclodextrin into poly(aspartic acid) matrix for adsorption and time-release of ibuprofen.

PubMed

Sun, Zhao-Yang; Shen, Ming-Xing; Yang, An-Wen; Liang, Cong-Qiang; Wang, Nan; Cao, Gui-Ping

2011-01-21

Biodegradable copolymers with molecule inclusion ability was prepared by introduction of β-cyclodextrin into poly(aspartic acid) matrices. The ibuprofen loading and dissolution properties of poly(aspartic acid)-β-cyclodextrin were investigated.

Sorption, desorption and displacement of ibuprofen, estrone, and 17β estradiol in wastewater irrigated and rainfed agricultural soils.

PubMed

Durán-Álvarez, Juan C; Prado, Blanca; Ferroud, Anouck; Juayerk, Narcedalia; Jiménez-Cisneros, Blanca

2014-03-01

Sorption and leaching potential of ibuprofen, estrone and 17β estradiol were tested in two agricultural soils: one irrigated using municipal wastewater and the other used in rainfed agriculture. Batch sorption-desorption experiments and undisturbed soil column assays were carried out using both soils to which were added a mixture of the target compounds. The three compounds were sorbed to a different extent by both soils: estrone>17β estradiol>ibuprofen. Higher sorption was observed in the irrigated soil, which was attributed to the accumulation of organic matter caused by wastewater irrigation. Desorption of hormones was hysteretic in the irrigated soil, while ibuprofen showed low hysteresis in both soils. Retardation of the compounds' displacement was consistent with the sorption pattern observed in the batch tests. Retardation factor (RF) was similar for the three compounds in the two tested soils, indicating that the target compounds are much more mobile in the soil columns than would be predicted based on their equilibrium sorption parameters. The results obtained in the experiments clarify the role of wastewater irrigated soils as a filter and degradation media for the target micropollutants. Copyright © 2013 Elsevier B.V. All rights reserved.

Handling Ibuprofen Increases Pain Tolerance and Decreases Perceived Pain Intensity in a Cold Pressor Test

PubMed Central

Rutchick, Abraham M.; Slepian, Michael L.

2013-01-01

Pain contributes to health care costs, missed work and school, and lower quality of life. Extant research on psychological interventions for pain has focused primarily on developing skills that individuals can apply to manage their pain. Rather than examining internal factors that influence pain tolerance (e.g., pain management skills), the current work examines factors external to an individual that can increase pain tolerance. Specifically, the current study examined the nonconscious influence of exposure to meaningful objects on the perception of pain. Participants (N = 54) completed a cold pressor test, examined either ibuprofen or a control object, then completed another cold pressor test. In the second test, participants who previously examined ibuprofen reported experiencing less intense pain and tolerated immersion longer (relative to baseline) than those who examined the control object. Theoretical and applied implications of these findings are discussed. PMID:23469170

Comparative efficacy and tolerability of pharmacological interventions for attention-deficit/hyperactivity disorder in children, adolescents and adults: protocol for a systematic review and network meta-analysis

PubMed Central

Cortese, Samuele; Adamo, Nicoletta; Mohr-Jensen, Christina; Hayes, Adrian J; Bhatti, Sahar; Carucci, Sara; Del Giovane, Cinzia; Atkinson, Lauren Z; Banaschewski, Tobias; Simonoff, Emily; Zuddas, Alessandro; Barbui, Corrado; Purgato, Marianna; Steinhausen, Hans-Christoph; Shokraneh, Farhad; Xia, Jun; Coghill, David

2017-01-01

Introduction Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles. Methods and analysis We will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. Ethics and

Pharmacology and pharmacogenetics of chemotherapeutic agents.

PubMed

Dawood, Shaheenah; Leyland-Jones, Brian

2009-06-01

The last decade the field of oncology has seen the introduction of several efficacious chemotherapeutic agents. However the benefits achieved have been modest at best. The choice of chemotherapeutic agent is often empirical and geared to fit the average patient with the result that approximately 40% of patients may be receiving the wrong drug. With greater understanding of the mechanisms behind the heterogeneity observed across patient populations, both in terms of efficacy and toxicity of a variety of therapeutic agents, research has now focused on individualizing treatment strategies by incorporating a combination of physiological variables, genetic characteristics and environmental factors together with the traditional tumor characteristics that currently drives clinical decision making. This review focuses on defining some of the principle components of personalized medicine. In addition we will review the pharmacological and pharmacogenetic predictors of toxic effects of chemotherapeutic agents drawing on examples of commonly used agents in oncology.

Pharmacological treatment for memory disorder in multiple sclerosis.

PubMed

He, Dian; Zhang, Yun; Dong, Shuai; Wang, Dongfeng; Gao, Xiangdong; Zhou, Hongyu

2013-12-17

This is an update of the Cochrane review "Pharmacologic treatment for memory disorder in multiple sclerosis" (first published in The Cochrane Library 2011, Issue 10).Multiple sclerosis (MS) is a chronic immune-mediated, inflammatory, demyelinating, neurodegenerative disorder of the central nervous system (CNS) and can cause both neurological and neuropsychological disability. Both demyelination and axonal and neuronal loss are believed to contribute to MS-related cognitive impairment. Memory disorder is one of the most frequent cognitive dysfunctions and presents a considerable burden to people with MS and to society due to the negative impact on function. A number of pharmacological agents have been evaluated in many existing randomised controlled trials for their efficacy on memory disorder in people with MS but the results were not consistent. To assess the absolute and comparative efficacy, tolerability and safety of pharmacological treatments for memory disorder in adults with MS. We searched the Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group Trials Register (24 July 2013), PsycINFO (January 1980 to 26 June 2013) and CBMdisc (1978 to 24 June 2013), and checked reference lists of identified articles, searched some relevant journals manually, registers of clinical trials and published abstracts of conference proceedings. All double-blind, randomised controlled parallel trials on pharmacological treatment versus placebo or one or more pharmacological treatments in adults with MS who had at least mild memory impairment (at 0.5 standard deviations below age- and sex-based normative data on a validated memory scale). We placed no restrictions regarding dose, route of administration and frequency; however, we only included trials with an administration duration of 12 weeks or greater. Two review authors independently assessed trial quality and extracted data. We discussed disagreements and resolved them by consensus among review

Pharmacologic considerations for Shuttle astronauts

NASA Technical Reports Server (NTRS)

Santy, Patricia A.; Bungo, Michael W.

1991-01-01

Medication usage by crewmembers in the preflight and inflight mission periods is common in the Shuttle Program. The most common medical reports for which medication is used are: space motion sickness (SMS), sleeplessness, headache, and backache. A number of medications are available in the Shuttle Medical Kit to treat these problems. Currently, astronauts test all frequently used medications before mission assignment to identify potential side-effects, problems related to performance, personal likes/dislikes, and individual therapeutic effect. However, microgravity-induced changes in drug pharmacokinetics, in combination with multiple operational factors, may significantly alter crewmember responses inflight. This article discusses those factors that may impact pharmacologic efficacy during Shuttle missions.

Occurrence of naproxen, ibuprofen, and diclofenac residues in wastewater and river water of KwaZulu-Natal Province in South Africa.

PubMed

Madikizela, Lawrence Mzukisi; Chimuka, Luke

2017-07-01

The present paper reports a detailed study that is based on the monitoring of naproxen, ibuprofen, and diclofenac in Mbokodweni River and wastewater treatment plants (WWTPs) located around the city of Durban in KwaZulu-Natal Province of South Africa. Target compounds were extracted from water samples using a multi-template molecularly imprinted solid-phase extraction prior to separation and quantification on a high-performance liquid chromatography equipped with photo diode array detector. The analytical method yielded the detection limits of 0.15, 1.00, and 0.63 μg/L for naproxen, ibuprofen, and diclofenac, respectively. Solid-phase extraction method was evaluated for its performance using deionized water samples that were spiked with 5 and 50 μg/L of target compounds. Recoveries were greater than 80% for all target compounds with RSD values in the range of 4.1 to 10%. Target compounds were detected in most wastewater and river water samples with ibuprofen being the most frequently detected pharmaceutical. Maximum concentrations detected in river water for naproxen, ibuprofen, and diclofenac were 6.84, 19.2, and 9.69 μg/L, respectively. The concentrations of target compounds found in effluent and river water samples compared well with some studies. The analytical method employed in this work is fast, selective, sensitive, and affordable; therefore, it can be used routinely to evaluate the occurrence of acidic pharmaceuticals in South African water resources.

PHARMACOLOGIC INTERVENTIONS FOR THE PREVENTION AND TREATMENT OF RETINOPATHY OF PREMATURITY

PubMed Central

Beharry, Kay D.; Valencia, G.B.; Lazzaro, D.R.; Aranda, J.V.

2016-01-01

Retinopathy of prematurity (ROP), a significant morbidity in prematurely born infants, is the most common cause of visual impairment and blindness in children and persists till adulthood. Strict control of oxygen therapy and prevention of intermittent hypoxia are key in the prevention of ROP, but pharmacologic interventions have decreased risk of ROP. Various drug classes such as methylxanthines (caffeine), VEGF inhibitors, anti-oxidants, and others have decreased ROP occurrence. The timing of pharmacologic intervention remains unsettled, but early prevention rather than controlling disease progression may be preferred. These drugs act through different mechanisms and synergistic approaches should be considered to maximize efficacy and safety. PMID:26831641

Pharmacological interactions of anti-inflammatory-analgesics in odontology.

PubMed

Gómez-Moreno, Gerardo; Guardia, Javier; Cutando, Antonio; Calvo-Guirado, José Luis

2009-02-01

In this second article we describe the more interesting pharmacological interactions in dental practice based on the prescription of analgesic narcotics, paracetamol and non-selective non-steroid anti-inflammatory drugs (NSAI) (which inhibit cyclooxigenase 1 -COX 1- and cyclooxigenase 2 -COX 2-) and selective NSAIs (COX 2 inhibitors). The importance of preventing the appearance of these pharmacological interactions is because these are medicaments prescribed daily in odontology for moderate pain treatment and inflammation in the oral cavity. Paracetamol can interact with warfarin and therefore care should be taken with chronic alcoholic patients. All NSAIs reduce renal blood flow and consequently are capable of reducing the efficacy of medicaments used for treating arterial hypertension, which act via a renal mechanism. Especial attention should be taken considering the risk of interaction between the antagonists of AT1 receptors of angiostensin II (ARAII) and the NSAIs.

Rosuvastatin: A Review of the Pharmacology and Clinical Effectiveness in Cardiovascular Disease

PubMed Central

Luvai, Ahai; Mbagaya, Wycliffe; Hall, Alistair S.; Barth, Julian H.

2012-01-01

Rosuvastatin is a new generation HMG-CoA reductase inhibitor which exhibits some unique pharmacologic and pharmacokinetic properties. It has low extrahepatic tissue penetration, low potential for CYP3A4 interactions and substantial LDL-C lowering capacity and therefore has distinct advantages. We conducted a Medline literature search to identify rosuvastatin papers published in English. In this review, we outline the pharmacology of rosuvastatin, highlighting its efficacy and safety. We also review the major clinical trials with reference to primary and secondary prevention, familial hypercholesterolaemia and comparison with other statins. Finally we address its place in clinical practice. PMID:22442638

The effectiveness of ibuprofen and lorazepam combination therapy in treating the symptoms of acute Migraine: A randomized clinical trial.

PubMed

Rad, Reza Ebrahimi; Ghaffari, Fatemeh; Fotokian, Zahra; Ramezani, Azadeh

2017-03-01

Migraine is a common, episodic and debilitating disease. The migraineur not only suffers from pain, but also lives with a diminished to poor quality of life. Several medicinal therapies are used to abate the debilitating symptoms of this disease. The present study was conducted to determine the effectiveness of Ibuprofen and Lorazepam combination therapy in treating the symptoms of acute migraine. The present randomized clinical trial study used the pretest-posttest design with three comparison treatments, to examine 90 patients with an average of two to six attacks per month and an initial diagnosis of migraine based on the International Headache Society (HIS) criteria. The study was conducted on patients during the first half of 2014 with a diagnosis of acute migraine attack who were referred to Babol Ayatollah Rouhani Hospital in Iran. The patients were randomly divided into three groups of 30. The first group was administered 200 mg Ibuprofen capsules, the second group 400 mg Ibuprofen capsules and the third group a combination of 200 mg Ibuprofen capsules and 1 mg Lorazepam tablets. The medications were taken in the presence of the researcher. A checklist was used to assess the severity of headache and other migraine symptoms such as nausea, vomiting, photophobia and phonophobia in the patients, before and two hours after the intervention. Data were analyzed in SPSS-18 using the Mann-Whitney test, the McNemar test, Wilcoxon's test, the NOVA and the Chi-squared test at the significance level of p<0.05, and power analysis with 30 patients in each group to perform this study was 0.8(1-β). The mean age of participants was reported as 52±8 years and the condition was more frequent in women (56%). All three treatment regimens reduced the severity of headache significantly in the patients (p<0.001); nevertheless, the combination therapy used, produced the lowest mean severity of headache (p<0.001). The highest reduction in nausea and vomiting was (3.3%). None of

Potential Benefits of Non-Pharmacological Therapies in Fibromyalgia

PubMed Central

Sueiro Blanco, F.; Estévez Schwarz, I.; Ayán, C.; Cancela, JM.; Martín, V.

2008-01-01

Fibromyalgia (FM) is an incurable common syndrome of non-articular origin, and with no effective treatment by now. A great deal of research has sought to assess the efficacy of different therapies, especially non-pharmacological and low-cost ones, in the reduction of the intensity of symptoms. Despite the availability of a wide range of alternative therapies nowadays, there is little scientific evidence of the potential benefits of most of them, with results being contradictories. The purpose of this paper is to review some of the less well known alternative therapies in FM treatment, to describe the more relevant clinical studies published in this matter, and to analyze the potential effects of the main alternative therapies, in order to verify their efficacy. PMID:19088863

Rheological behavior and Ibuprofen delivery applications of pH responsive composite alginate hydrogels.

PubMed

Jabeen, Suraya; Maswal, Masrat; Chat, Oyais Ahmad; Rather, Ghulam Mohammad; Dar, Aijaz Ahmad

2016-03-01

Synthesis and structural characterization of hydrogels composed of sodium alginate, polyethylene oxide and acrylic acid with cyclodextrin as the hydrocolloid prepared at different pH values is presented. The hydrogels synthesized show significant variations in rheological properties, drug encapsulation capability and release kinetics. The hydrogels prepared at lower pH (pH 1) are more elastic, have high tensile strength and remain almost unaffected by varying temperature or frequency. Further, their Ibuprofen encapsulation capacity is low and releases it slowly. The hydrogel prepared at neutral pH (pH 7) is viscoelastic, thermo-reversible and also exhibits sol-gel transition on applying frequency and changing temperature. It shows highest Ibuprofen encapsulation capacity and also optimum drug release kinetics. The hydrogel prepared at higher pH (pH 12) is more viscous, has low tensile strength, is unstable to change in temperature and has fast drug release rate. The study highlights the pH responsiveness of three composite alginate hydrogels prepared under different conditions to be employed in drug delivery applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Is systems pharmacology ready to impact upon therapy development? A study on the cholesterol biosynthesis pathway

PubMed Central

Benson, Helen E; Sharman, Joanna L; Mpamhanga, Chido P; Parton, Andrew; Southan, Christopher; Harmar, Anthony J; Ghazal, Peter

2017-01-01

Background and Purpose An ever‐growing wealth of information on current drugs and their pharmacological effects is available from online databases. As our understanding of systems biology increases, we have the opportunity to predict, model and quantify how drug combinations can be introduced that outperform conventional single‐drug therapies. Here, we explore the feasibility of such systems pharmacology approaches with an analysis of the mevalonate branch of the cholesterol biosynthesis pathway. Experimental Approach Using open online resources, we assembled a computational model of the mevalonate pathway and compiled a set of inhibitors directed against targets in this pathway. We used computational optimization to identify combination and dose options that show not only maximal efficacy of inhibition on the cholesterol producing branch but also minimal impact on the geranylation branch, known to mediate the side effects of pharmaceutical treatment. Key Results We describe serious impediments to systems pharmacology studies arising from limitations in the data, incomplete coverage and inconsistent reporting. By curating a more complete dataset, we demonstrate the utility of computational optimization for identifying multi‐drug treatments with high efficacy and minimal off‐target effects. Conclusion and Implications We suggest solutions that facilitate systems pharmacology studies, based on the introduction of standards for data capture that increase the power of experimental data. We propose a systems pharmacology workflow for the refinement of data and the generation of future therapeutic hypotheses. PMID:28910500

Sarcopenia: Pharmacology of Today and Tomorrow

PubMed Central

Abreu, Eduardo L.

2012-01-01

Sarcopenia remains largely undiagnosed and undertreated because of the lack of a universally accepted definition, effective ways to measure it, and identification of the outcomes that should guide treatment efficacy. An ever-growing number of clinicians and researchers along with funding and regulatory agencies have gradually recognized that sarcopenia is a human condition that requires both prevention and treatment. In this article, we review sarcopenia and its common and less known pharmacological treatments, attempt to define sarcopenia in its broader context, and present some new ideas for potential future treatment for this devastating condition. PMID:22929991

Synthetic Cannabinoids: Pharmacology, Behavioral Effects, and Abuse Potential

PubMed Central

Tai, Sherrica; Fantegrossi, William E.

2015-01-01

Cannabis has been used throughout the world for centuries. The psychoactive effects of cannabis are largely attributable to Δ9-tetrahydrocannabinol (Δ9-THC), the prototypical cannabinoid that occurs naturally in the plant. More recently, chemically- and pharmacologically-distinct synthetic cannabinoids (SCBs) have emerged as drugs of abuse. As compared to Δ9-THC, the distinct structures of these compounds allow them to avoid legal restrictions (at least initially) and detection in standard drug screens. This has contributed to the popularity of SCBs among drug users who seek to avoid positive drug screens. Importantly, the distinct structures of the SCBs also typically result in increased affinity for and efficacy at cannabinoid CB1 receptors, which are thought to be responsible for the psychoactive effects of Δ9-THC and its analogues. Accordingly, it seems likely that these more powerful cannabimimetic effects could result in increased adverse reactions and toxicities not elicited by Δ9-THC in cannabis. Animal models useful for the study of emerging SCBs include the cannabinoid tetrad, drug discrimination, and assays of tolerance, dependence, and withdrawal. However, these in vivo procedures have not been particularly informative with regards to drug efficacy, where the majority of SCB effects are comparable to those of Δ9-THC. In contrast, essentially all in vitro measures of drug efficacy confirm Δ9-THC as a relatively weak CB1 partial agonist, while the majority of the SCBs detected in commercial preparations are full agonists at the CB1 receptor. As use of these emerging SCBs continues to rise, there is an urgent need to better understand the pharmacology and toxicology of these novel compounds. PMID:26413452

Cannabis Pharmacology: The Usual Suspects and a Few Promising Leads.

PubMed

Russo, Ethan B; Marcu, Jahan

2017-01-01

The golden age of cannabis pharmacology began in the 1960s as Raphael Mechoulam and his colleagues in Israel isolated and synthesized cannabidiol, tetrahydrocannabinol, and other phytocannabinoids. Initially, THC garnered most research interest with sporadic attention to cannabidiol, which has only rekindled in the last 15 years through a demonstration of its remarkably versatile pharmacology and synergy with THC. Gradually a cognizance of the potential of other phytocannabinoids has developed. Contemporaneous assessment of cannabis pharmacology must be even far more inclusive. Medical and recreational consumers alike have long believed in unique attributes of certain cannabis chemovars despite their similarity in cannabinoid profiles. This has focused additional research on the pharmacological contributions of mono- and sesquiterpenoids to the effects of cannabis flower preparations. Investigation reveals these aromatic compounds to contribute modulatory and therapeutic roles in the cannabis entourage far beyond expectations considering their modest concentrations in the plant. Synergistic relationships of the terpenoids to cannabinoids will be highlighted and include many complementary roles to boost therapeutic efficacy in treatment of pain, psychiatric disorders, cancer, and numerous other areas. Additional parts of the cannabis plant provide a wide and distinct variety of other compounds of pharmacological interest, including the triterpenoid friedelin from the roots, canniprene from the fan leaves, cannabisin from seed coats, and cannflavin A from seed sprouts. This chapter will explore the unique attributes of these agents and demonstrate how cannabis may yet fulfil its potential as Mechoulam's professed "pharmacological treasure trove." © 2017 Elsevier Inc. All rights reserved.

Channeling in the Use of Nonprescription Paracetamol and Ibuprofen in an Electronic Medical Records Database: Evidence and Implications.

PubMed

Weinstein, Rachel B; Ryan, Patrick; Berlin, Jesse A; Matcho, Amy; Schuemie, Martijn; Swerdel, Joel; Patel, Kayur; Fife, Daniel

2017-12-01

Over-the-counter analgesics such as paracetamol and ibuprofen are among the most widely used, and having a good understanding of their safety profile is important to public health. Prior observational studies estimating the risks associated with paracetamol use acknowledge the inherent limitations of these studies. One threat to the validity of observational studies is channeling bias, i.e. the notion that patients are systematically exposed to one drug or the other, based on current and past comorbidities, in a manner that affects estimated relative risk. The aim of this study was to examine whether evidence of channeling bias exists in observational studies that compare paracetamol with ibuprofen, and, if so, the extent to which confounding adjustment can mitigate this bias. In a cohort of 140,770 patients, we examined whether those who received any paracetamol (including concomitant users) were more likely to have prior diagnoses of gastrointestinal (GI) bleeding, myocardial infarction (MI), stroke, or renal disease than those who received ibuprofen alone. We compared propensity score distributions between drugs, and examined the degree to which channeling bias could be controlled using a combination of negative control disease outcome models and large-scale propensity score matching. Analyses were conducted using the Clinical Practice Research Datalink. The proportions of prior MI, GI bleeding, renal disease, and stroke were significantly higher in those prescribed any paracetamol versus ibuprofen alone, after adjusting for sex and age. We were not able to adequately remove selection bias using a selected set of covariates for propensity score adjustment; however, when we fit the propensity score model using a substantially larger number of covariates, evidence of residual bias was attenuated. Although using selected covariates for propensity score adjustment may not sufficiently reduce bias, large-scale propensity score matching offers a novel approach to

The Risk of Major NSAID Toxicity with Celecoxib, Ibuprofen, or Naproxen: A Secondary Analysis of the PRECISION Trial.

PubMed

Solomon, Daniel H; Husni, M Elaine; Libby, Peter A; Yeomans, Neville D; Lincoff, A Michael; Lϋscher, Thomas F; Menon, Venu; Brennan, Danielle M; Wisniewski, Lisa M; Nissen, Steven E; Borer, Jeffrey S

2017-12-01

The relative safety of long-term use of nonsteroidal anti-inflammatory drugs is unclear. Patients and providers are interested in an integrated view of risk . We examined the risk of major nonsteroidal anti-inflammatory drug toxicity in the PRECISION trial. We conducted a post hoc analysis of a double-blind, randomized, controlled, multicenter trial enrolling 24,081 patients with osteoarthritis or rheumatoid arthritis at moderate or high cardiovascular risk. Patients were randomized to receive celecoxib 100 to 200 mg twice daily, ibuprofen 600 to 800 mg thrice daily, or naproxen 375 to 500 mg twice daily. All patients were provided with a proton pump inhibitor. The outcome was major nonsteroidal anti-inflammatory drug toxicity, including time to first occurrence of major adverse cardiovascular events, important gastrointestinal events, renal events, and all-cause mortality. During follow-up, 4.1% of subjects sustained any major toxicity in the celecoxib arm, 4.8% in the naproxen arm, and 5.3% in the ibuprofen arm. Analyses adjusted for aspirin use and geographic region found that subjects in the naproxen arm had a 20% (95% CI 4-39) higher risk of major toxicity than celecoxib users and that 38% (95% CI 19-59) higher risk. These risks translate into numbers needed to harm of 135 (95% CI, 72-971) for naproxen and 82 (95% CI, 53-173) for ibuprofen, both compared with celecoxib. Among patients with symptomatic arthritis who had moderate to high risk of cardiovascular events, approximately 1 in 20 experienced a major toxicity over 1 to 2 years. Patients using naproxen or ibuprofen experienced significantly higher risk of major toxicity than those using celecoxib. Copyright © 2017 Elsevier Inc. All rights reserved.

Joint Inflammation and Early Degeneration Induced by High-Force Reaching Are Attenuated by Ibuprofen in an Animal Model of Work-Related Musculoskeletal Disorder

PubMed Central

Driban, Jeffrey B.; Barr, Ann E.; Amin, Mamta; Sitler, Michael R.; Barbe, Mary F.

2011-01-01

We used our voluntary rat model of reaching and grasping to study the effect of performing a high-repetition and high-force (HRHF) task for 12 weeks on wrist joints. We also studied the effectiveness of ibuprofen, administered in the last 8 weeks, in attenuating HRHF-induced changes in these joints. With HRHF task performance, ED1+ and COX2+ cells were present in subchondral radius, carpal bones and synovium; IL-1alpha and TNF-alpha increased in distal radius/ulna/carpal bones; chondrocytes stained with Terminal deoxynucleotidyl Transferase- (TDT-) mediated dUTP-biotin nick end-labeling (TUNEL) increased in wrist articular cartilages; superficial structural changes (e.g., pannus) and reduced proteoglycan staining were observed in wrist articular cartilages. These changes were not present in normal controls or ibuprofen treated rats, although IL-1alpha was increased in reach limbs of trained controls. HRHF-induced increases in serum C1,2C (a biomarker of collagen I and II degradation), and the ratio of collagen degradation to synthesis (C1,2C/CPII; the latter a biomarker of collage type II synthesis) were also attenuated by ibuprofen. Thus, ibuprofen treatment was effective in attenuating HRHF-induced inflammation and early articular cartilage degeneration. PMID:21403884

Parameters for defining efficacy in fracture healing

PubMed Central

Shisha, Tamas

2010-01-01

Complications of the bone-healing process, especially in elderly, osteoporotic patients, are cause of important medical and economical burden. At the same time, there is no clinical study today to have shown the efficacy of a pharmacological treatment to enhance fracture repair. The author analyzes the potential criteria that could be used for the evaluation of treatment efficacy to enhance fracture healing in the frame of a clinical study. PMID:22461284

Short-term exposure and long-term consequences of neonatal exposure to Δ(9)-tetrahydrocannabinol (THC) and ibuprofen in mice.

PubMed

Philippot, Gaëtan; Nyberg, Fred; Gordh, Torsten; Fredriksson, Anders; Viberg, Henrik

2016-07-01

Both Δ(9)-tetrahydrocannabinol (THC) and ibuprofen have analgesic properties by interacting with the cannabinoid receptor type 1 (CB1R) and the cyclooxygenase (COX) systems, respectively. Evaluation of these analgesics is important not only clinically, since they are commonly used during pregnancy and lactation, but also to compare them with acetaminophen, with a known interaction with both CB1R and the COX systems. Short-term exposure of neonatal rodents to acetaminophen during the first weeks of postnatal life, which is comparable with a period from the third trimester of pregnancy to the first years of postnatal life in humans, induces long-term behavioral disturbances. This period, called the brain growth spurt (BGS) and is characterized by series of rapid and fundamental changes and increased vulnerability, peaks around postnatal day (PND) 10 in mice. We therefore exposed male NMRI mice to either THC or ibuprofen on PND 10. At 2 months of age, the mice were subjected to a spontaneous behavior test, consisting of a 60min recording of the variables locomotion, rearing and total activity. Mice exposed to THC, but not ibuprofen, exhibited altered adult spontaneous behavior and habituation capability in a dose-dependent manner. This highlights the potency of THC as a developmental neurotoxicant, since a single neonatal dose of THC was enough to affect adult cognitive function. The lack of effect from ibuprofen also indicates that the previously seen developmental neurotoxicity of acetaminophen is non-COX-mediated. These results might be of importance in future research as well as in the ongoing risk/benefit assessment of THC. Copyright © 2016. Published by Elsevier B.V.

Association of Placebo, Indomethacin, Ibuprofen, and Acetaminophen With Closure of Hemodynamically Significant Patent Ductus Arteriosus in Preterm Infants: A Systematic Review and Meta-analysis.

PubMed

Mitra, Souvik; Florez, Ivan D; Tamayo, Maria E; Mbuagbaw, Lawrence; Vanniyasingam, Thuva; Veroniki, Areti Angeliki; Zea, Adriana M; Zhang, Yuan; Sadeghirad, Behnam; Thabane, Lehana

2018-03-27

Despite increasing emphasis on conservative management of patent ductus arteriosus (PDA) in preterm infants, different pharmacotherapeutic interventions are used to treat those developing a hemodynamically significant PDA. To estimate the relative likelihood of hemodynamically significant PDA closure with common pharmacotherapeutic interventions and to compare adverse event rates. The databases of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until August 15, 2015, and updated on December 31, 2017, along with conference proceedings up to December 2017. Randomized clinical trials that enrolled preterm infants with a gestational age younger than 37 weeks treated with intravenous or oral indomethacin, ibuprofen, or acetaminophen vs each other, placebo, or no treatment for a clinically or echocardiographically diagnosed hemodynamically significant PDA. Data were independently extracted in pairs by 6 reviewers and synthesized with Bayesian random-effects network meta-analyses. Primary outcome: hemodynamically significant PDA closure; secondary: included surgical closure, mortality, necrotizing enterocolitis, and intraventricular hemorrhage. In 68 randomized clinical trials of 4802 infants, 14 different variations of indomethacin, ibuprofen, or acetaminophen were used as treatment modalities. The overall PDA closure rate was 67.4% (2867 of 4256 infants). A high dose of oral ibuprofen was associated with a significantly higher odds of PDA closure vs a standard dose of intravenous ibuprofen (odds ratio [OR], 3.59; 95% credible interval [CrI], 1.64-8.17; absolute risk difference, 199 [95% CrI, 95-258] more per 1000 infants) and a standard dose of intravenous indomethacin (OR, 2.35 [95% CrI, 1.08-5.31]; absolute risk difference, 124 [95% CrI, 14-188] more per 1000 infants). Based on the ranking statistics, a high dose of oral ibuprofen ranked as the best pharmacotherapeutic option for PDA closure (mean surface under the

Ibuprofen and/or paracetamol (acetaminophen) for pain relief after surgical removal of lower wisdom teeth, a Cochrane systematic review.

PubMed

Bailey, E; Worthington, H; Coulthard, P

2014-04-01

This paper compares 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. In this systematic review only randomised controlled double-blinded clinical trials were included. We calculated the proportion of patients with at least 50% pain relief at 2 and 6 hours post dosing, along with the proportion of participants using rescue medication at 6 and 8 hours. Adverse events were also analysed. Data was meta-analysed where possible. Seven studies were included with a total of 2,241 participants enrolled. Ibuprofen 400 mg is superior to 1,000 mg paracetamol with a risk ratio for at least 50% pain relief at 6 hours of 1.47 (95% confidence interval [CI] 1.28 to 1.69). For the combined drug, the risk ratio for at least 50% maximum pain relief over 6 hours is 1.77 (95% CI 1.32 to 2.39) based on total pain relief (TOTPAR) data. There is high quality evidence that ibuprofen is superior to paracetamol. The novel combination drug shows encouraging results when compared to the single drugs (based on two trials).

[Pharmacological aspects of pain research in Germany].

PubMed

Niederberger, E; Kuner, R; Geißlinger, G

2015-10-01

In spite of several approved analgesics, the therapy of pain still constitutes a challenge due to the fact that the drugs do not exert sufficient efficacy or are associated with severe side effects. Therefore, the development of new and improved painkillers is still of great importance. A number of highly qualified scientists in Germany are investigating signal transduction pathways in pain, effectivity of new drugs and the so far incompletely investigated mechanisms of well-known analgesics in preclinical and clinical studies. The highlights of pharmacological pain research in Germany are summarized in this article.

Supramolecular separation mechanism of pentafluorophenyl column using ibuprofen and omeprazole as markers: LC-MS and simulation study.

PubMed

Hussain, Afzal; AlAjmi, Mohamed F; Ali, Imran

2018-06-01

The pentafluorophenyl (PFP) column is emerging as a new advancement in separation science to analyze a wide range of analytes and, thus, its separation mechanism at supramolecular level is significant. We developed a mechanism for the separation of ibuprofen and omeprazole using different combinations (ranging from 50:50 to 60:40) of water-acetonitrile containing 0.1% formic acid as the mobile phase. The column used was Waters Acquity UPLC HSS PFP (75 × 2.1 mm, 1.8 μm). The reverse order of elution was observed in different combinations of the mobile phases. The docking study indicated hydrogen bonding between ibuprofen and PFP stationary phase (binding energy was -11.30 kJ/mol). Separation at PFP stationary phase is controlled by hydrogen bonding along with π-π interactions. This stationary phase may be used to analyze both aromatic and aliphatic analytes. The developed mechanism will be useful to separate various analytes by considering the possible interactions, leading to saving of energy, time and money. In addition, this work will be highly useful in preparative chromatography where separation is the major problem at a large scale. Moreover, the developed LC-MS-QTOF method may be used to analyze ibuprofen and omeprazole in an unknown sample owing to the low value of detection limits. Copyright © 2018 John Wiley & Sons, Ltd.

Repeated Courses of Oral Ibuprofen in Premature Infants with Patent Ductus Arteriosus: Efficacy and Safety.

PubMed

Olgun, Haşim; Ceviz, Naci; Kartal, İbrahim; Caner, İbrahim; Karacan, Mehmet; Taştekin, Ayhan; Becit, Necip

2017-02-01

There are limited data about the results of repeated oral ibuprofen (OIBU) treatment. This study aimed to describe patent ductus arteriosus (PDA) closure rates and adverse events after repeated courses of OIBU in premature infants with PDA. Preterm infants with hemodynamically significant (hs)PDA were enrolled in the study. If the first course of OIBU treatment failed, a second and, if required, third course was administered. A total of 100 patients received OIBU. In six patients, treatment could not be completed due to death (n=3) and side effects (n=3). In three patients, adverse effects related to OIBU (thrombocytopenia and impairment of renal function) developed during the first course. During the second and third courses, no new adverse event occurred. After all courses, the PDA closure rate was determined as 88%. The rate was 71% after the first course, 40% after the second course, and 35% after the third course. Although the second course resulted in a significant increase in the closure rate (p<0.05), the rate did not increase significantly with the third course (p>0.05). The mean postnatal age at the start of the first dose of OIBU was not significantly different among the responders and non-responders to the first course (p>0.05). Clinical characteristics did not affect the closure rate significantly. The number of courses did not have a significant effect on death, when gestational age and birth weight were used as covariates [p=0.867, Exp(B)=0.901, 95% confidence interval=0.264-3.1]. A second course of OIBU seems effective and safe for use in preterm infants with hsPDA. Although a third course of OIBU results in PDA closure in some additional patients, the difference is not significant. Thus, surgical ligation should be considered after the second course, especially in patients with signs of severe heart failure. Copyright © 2016. Published by Elsevier B.V.

Pharmacologic interventions for the prevention and treatment of retinopathy of prematurity.

PubMed

Beharry, Kay D; Valencia, Gloria B; Lazzaro, Douglas R; Aranda, Jacob V

2016-04-01

Retinopathy of prematurity (ROP), a significant morbidity in prematurely born infants, is the most common cause of visual impairment and blindness in children and persists till adulthood. Strict control of oxygen therapy and prevention of intermittent hypoxia are the keys in the prevention of ROP, but pharmacologic interventions have decreased risk of ROP. Various drug classes such as methylxanthines (caffeine), VEGF inhibitors, antioxidants, and others have decreased ROP occurrence. The timing of pharmacologic intervention remains unsettled, but early prevention rather than controlling disease progression may be preferred. These drugs act through different mechanisms, and synergistic approaches should be considered to maximize efficacy and safety. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Microwave generated solid dispersions containing Ibuprofen.

PubMed

Moneghini, Mariarosa; Bellich, Barbara; Baxa, Pietro; Princivalle, Francesco

2008-09-01

The purpose of this study was to apply the attractive technique of the microwaves irradiation (MW) for the preparation of solvent-free solid dispersions (SD). In particular, the microwave technology has been considered in order to prepare an enhanced release dosage form for the poorly soluble drug Ibuprofen (IBU), employing PVP/VA 60/40 (PVP/VA 64) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as hydrophilic carriers. Their physico-chemical characteristics and dissolution properties were compared to the corresponding physical mixtures and the drug alone. The results of physico-chemical characterization attested a correspondence of the solid state of the drug before and after irradiation treatment and that an amorphous form of the drug was obtained. This result, together with the presence of the hydrophilic polymers determined a remarkable enhancement of the in vitro dissolution rate of the drug suggesting that the microwave technique could be considered as a new and interesting method to prepare drug-polymer systems.

Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial

PubMed Central

Peter, Elizabeth A.; Janssen, Patricia A.; Grange, Caroline S.; Douglas, M. Joanne

2001-01-01

Background Pain from episiotomy or tearing of perineal tissues during childbirth is often poorly treated and may be severe. This randomized double-blind controlled trial was performed to compare the effectiveness, side effects and cost of, and patient preference for, 2 analgesics for the management of postpartum perineal pain. Methods A total of 237 women who gave birth vaginally with episiotomy or a third- or fourth-degree tear between August 1995 and November 1996 at a tertiary-level teaching and referral centre for obstetric care in Vancouver were randomly assigned to receive either ibuprofen (400 mg) (n = 127) or acetaminophen (600 mg) with codeine (60 mg) and caffeine (15 mg) (Tylenol No. 3) (n = 110), both given orally every 4 hours as necessary. Pain ratings were recorded before the first dose and at 1, 2, 3, 4, 12 and 24 hours after the first dose on a 10-cm visual analogue scale. Side effects and overall opinion were assessed at 24 hours. Results Ibuprofen and acetaminophen with codeine had similar analgesic properties in the first 24 hours post partum (mean pain rating 3.4 and 3.3, mean number of doses in 24 hours 3.4 and 3.3, and proportion of treatment failures 13.8% [16/116] and 16.0% [16/100] respectively). Significantly fewer subjects in the ibuprofen group than in the acetaminophen with codeine group experienced side effects (52.4% v. 71.7%) (p = 0.006). There were no significant differences in overall patient satisfaction between the 2 groups. The major determinant of pain intensity was forceps-assisted delivery. Overall, 78% of the treatment failures were in women with forceps-assisted deliveries. Interpretation Since the 2 analgesics were rated similarly, ibuprofen may be the preferred choice because it is less expensive and requires less nursing time to dispense. Further studies need to address improved analgesia for women with forceps-assisted deliveries. PMID:11706909

Simple and sensitive HPLC method with fluorescence detection for the measurement of ibuprofen in rat plasma: application to a long-lasting dosage form.

PubMed

Hassan, Ahmed Sheikh; Sapin, Anne; Ubrich, Nathalie; Maincent, Philippe; Bolzan, Claire; Leroy, Pierre

2008-10-01

A simple and sensitive high-performance liquid chromatography (HPLC) assay applied to the measurement of ibuprofen in rat plasma has been developed. Two parameters have been investigated to improve ibuprofen detectability using fluorescence detection: variation of mobile phase pH and the use of beta-cyclodextrin (beta-CD). Increasing the pH value from 2.5 to 6.5 and adding 5 mM beta-CD enhanced the fluorescence signal (lambda(exc) = 224 nm; lambda(em) = 290 nm) by 2.5 and 1.3-fold, respectively, when using standards. In the case of plasma samples, only pH variation significantly lowered detection and quantification limits, down to 10 and 35 ng/mL, respectively. Full selectivity was obtained with a single step for plasma treatment, that is, protein precipitation with acidified acetonitrile. The validated method was applied to a pharmacokinetic study of ibuprofen encapsulated in microspheres and subcutaneously administered to rats.

Pharmacological treatment of diabetes in older people.

PubMed

Valencia, W M; Florez, H

2014-12-01

The pharmacological management of diabetes in older people is complex and challenging. It requires a comprehensive understanding of the individual beyond the diabetes itself. Through the ageing years, the older individual presents with diabetes-related and non-related comorbidities and complications, develops functional limitations and psychological issues, and may lack social support and access to care. A disturbance in these categories, known as the four geriatric domains, will negatively affect diabetes self-management and self-efficacy, leading to poor outcomes and complications. Furthermore, older people with diabetes may be more interested in the management of other chronic conditions such as pain or impaired mobility, and diabetes may be lower in their list of priorities. Proper education must be provided to the older individual and caregivers, with continuous monitoring and counselling, especially when pharmacological interventions offer risks of side effects, adverse reactions and interactions with other medications. Informed shared medical decisions will help to improve adherence to the regimen; however, such discussions ought to be based on the best evidence available, which is unfortunately limited in this age group. We performed a review focused on pharmacological agents and summarize current evidence on their use for the treatment of diabetes in older people. We encourage clinicians to investigate and incorporate the four geriatrics domains in the selection and monitoring of these agents. © 2014 John Wiley & Sons Ltd.

Pharmacological analyses of learning and memory in zebrafish (Danio rerio).

PubMed

Bailey, Jordan M; Oliveri, Anthony N; Levin, Edward D

2015-12-01

Over the last decade, zebrafish (Danio rerio) have become valuable as a complementary model in behavioral pharmacology, opening a new avenue for understanding the relationships between drug action and behavior. This species offers a useful intermediate approach bridging the gap between in vitro studies and traditional mammalian models. Zebrafish offer great advantages of economy compared to their rodent counterparts, their complex brains and behavioral repertoire offer great translational potential relative to in vitro models. The development and validation of a variety of tests to measure behavior, including cognition, in zebrafish have set the stage for the use of this animal for behavioral pharmacology studies. This has led to research into the basic mechanisms of cognitive function as well as screening for potential cognition-improving drug therapies, among other lines of research. As with all models, zebrafish have limitations, which span pharmacokinetic challenges to difficulties quantifying behavior. The use, efficacy and limitations associated with a zebrafish model of cognitive function are discussed in this review, within the context of behavioral pharmacology. Copyright © 2015 Elsevier Inc. All rights reserved.

Release kinetics and cell viability of ibuprofen nanocrystals produced by melt-emulsification.

PubMed

Fernandes, A R; Dias-Ferreira, J; Cabral, C; Garcia, M L; Souto, E B

2018-06-01

The clinical use of poorly water-soluble drugs has become a big challenge in pharmaceutical development due to the compromised bioavailability of the drugs in vivo. Nanocrystals have been proposed as a formulation strategy to improve the dissolution properties of these drugs. The benefits of using nanocrystals in drug delivery, when compared to other nanoparticles, are related to their production facilities, simple structure, and suitability for a variety of administration routes. High pressure homogenization (HPH) is the most promising production process, which can be employed at low or high temperatures. Ibuprofen nanocrystals with a mean size below 175 nm, and polydispersity below 0.18, have been produced by melt-emulsification, followed by HPH. Two nanocrystal formulations, differing on the surfactant composition, have been produced, their in vitro ibuprofen release tested in Franz diffusion cells and adjusted to several kinetic models (zero order, first order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas, Baker-Lonsdale and Weibull model). Cell viability was assessed at 3, 6 and 24 h of incubation on human epithelial colorectal cells (Caco-2) by AlamarBlue ® colorimetric assay. For both formulations, Caco-2 cells viability was dependent on the drug concentration and time of exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

Influence of crystal habit on the compression and densification mechanism of ibuprofen

NASA Astrophysics Data System (ADS)

Di Martino, Piera; Beccerica, Moira; Joiris, Etienne; Palmieri, Giovanni F.; Gayot, Anne; Martelli, Sante

2002-08-01

Ibuprofen was recrystallized from several solvents by two different methods: addition of a non-solvent to a drug solution and cooling of a drug solution. Four samples, characterized by different crystal habit, were selected: sample A, sample E and sample T, recrystallized respectively from acetone, ethanol and THF by addition of water as non-solvent and sample M recrystallized from methanol by temperature decrease. By SEM analysis, sample were characterized with the respect of their crystal habit, mean particle diameter and elongation ratio. Sample A appears stick-shaped, sample E acicular with lamellar characteristics, samples T and M polyhedral. DSC and X-ray diffraction studies permit to exclude a polymorphic modification of ibuprofen during crystallization. For all samples micromeritics properties, densification behaviour and compression ability was analysed. Sample M shows a higher densification tendency, evidenciated by its higher apparent and tapped particle density. The ability to densificate is also pointed out by D0' value of Heckel's plot, which indicate the rearrangement of original particles at the initial stage of compression. This fact is related to the crystal habit of sample M, which is characterized by strongly smoothed coins. The increase in powder bed porosity permits a particle-particle interaction of greater extent during the subsequent stage of compression, which allows higher tabletability and compressibility.

A freeze-dried injectable form of ibuprofen: development and optimisation using response surface methodology.

PubMed

Kagkadis, K A; Rekkas, D M; Dallas, P P; Choulis, N H

1996-01-01

In this study a complex of Ibuprofen and b-Hydroxypropylcyclodextrin was prepared employing a freeze drying method. The production parameters and the final specifications of this product were optimized by using response surface methodology. The results show that the freeze dried complex meets the requirements for solubility to be considered as a possible injectable form.

Pterocarpus santalinus: a traditional herbal drug as a protectant against ibuprofen induced gastric ulcers.

PubMed

Narayan, Shoba; Devi, R S; Srinivasan, P; Shyamala Devi, C S

2005-11-01

The ethanol extract of Pterocarpus santalinus (PS) was evaluated for gastroprotection in rats using ibuprofen as the induction model. Rats treated with PS (100-400 mg/kg) showed a significant reduction in gastric lesions. PS at a dose of 200 mg/kg was found to be the minimum effective dose and hence further studies with that dose were carried out. PS treatment increased the LDH activity and decreased the lipid peroxidation levels. The extract had the ability to increase the antioxidant enzymes SOD, CAT and GPx when compared with the untreated but induced rats. The membrane bound ATPases - H(+)K(+)ATPase, Na(+)K(+)ATPase and Ca(2+)ATPases were increased upon the induction with ulcerogen. The treated group showed a decrease in the activities of these enzymes and also had the ability to restore the sodium and potassium ion concentrations to near normal levels, which were altered by ibuprofen mediated acid stimulation. The results suggest that the antiulcer properties of PS could traced to its acid inhibiting potential, antioxidant activity and the ability to maintain functional integrity of the cell membranes.

Randomised controlled trials of psychological & pharmacological treatments for body dysmorphic disorder: A systematic review.

PubMed

Phillipou, Andrea; Rossell, Susan L; Wilding, Helen E; Castle, David J

2016-11-30

Treatment for body dysmorphic disorder (BDD) often involves a combination of psychological and pharmacological interventions. However, only a small number of randomised controlled trials (RCTs) have been undertaken examining the efficacy of different therapeutic interventions. The aim of this study was to systematically review the RCTs involving psychological and pharmacological interventions for the treatment of BDD. The literature was searched to June 2015, and studies were included if they were written in English, empirical research papers published in peer-review journals, specifically assessed BDD patients, and involved a RCT assessing BDD symptoms pre- and post-intervention. Nine studies were identified: six involving psychological and three involving pharmacological interventions. Cognitive behaviour therapy, metacognitive therapy and selective serotonin reuptake inhibitors were identified as treatments with potential benefit. The small number of RCTs and the heterogeneity of findings emphasises the need for more high quality RCTs assessing both psychological and pharmacological interventions for BDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

COMPARISON OF THE EFFECTS OF NICOTINE AND NON-PHARMACOLOGICAL MANIPULATIONS ON REPEATED ACQUISITION IN RATS.

EPA Science Inventory

Non-pharmacological manipulations may be useful in identifying the behavioral mechanisms of drug action. We therefore compared the effect of nicotine with several manipulations of reinforcer efficacy on the repeated acquisition of response sequences in rats. Adult male Long-Eva...

Nalmefene for the management of alcohol dependence: review on its pharmacology, mechanism of action and meta-analysis on its clinical efficacy.

PubMed

Mann, Karl; Torup, Lars; Sørensen, Per; Gual, Antoni; Swift, Robert; Walker, Brendan; van den Brink, Wim

2016-12-01

Nalmefene, a mu- and delta-opioid receptor (MOR, DOR) antagonist and a partial kappa-opioid receptor (KOR) agonist, is approved in the European Union and other countries for the reduction of alcohol consumption in alcohol dependent patients with a high drinking risk level according to WHO ("target population"). This review presents an overview of nalmefene׳s pharmacology, its mechanisms of action and a meta-analysis on its efficacy in reducing alcohol consumption. The review was based on a systematic search of the literature. Random effects meta-analyses were performed on published and unpublished trials directed at drinking reduction using the changes in heavy drinking days (HDDs) and daily total alcohol consumption (TAC) from baseline to the primary endpoint. For each included study and each dose, Hedges' g was used as an unbiased estimator of the standardised mean differences between nalmefene and placebo. Preclinical data suggests that nalmefene counters alcohol-induced dysregulations of the MOR/endorphine and the KOR/dynorphin system. Evidence further suggests that reduced alcohol consumption is an effective treatment strategy that appeals to patients not ready for abstinence. Finally, meta-analyses confirmed the efficacy of 20mg nalmefene for reducing HDDs in the ITT population (Hedge׳s g=-0.20; 95% CI -0.30 to -0.09) and the target population (Hedge׳s g=-0.33; 95% CI -0.48 to -0.18). Similar results were seen for TAC. Several meta-analyses, including this new meta-analysis, support nalmefene׳s efficacy in reducing alcohol consumption. In conclusion, because it does not require abstinence, this treatment has the potential to motivate more patients for treatment and thus helps to address a major public health concern. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Comparative efficacy and tolerability of pharmacological interventions for attention-deficit/hyperactivity disorder in children, adolescents and adults: protocol for a systematic review and network meta-analysis.

PubMed

Cortese, Samuele; Adamo, Nicoletta; Mohr-Jensen, Christina; Hayes, Adrian J; Bhatti, Sahar; Carucci, Sara; Del Giovane, Cinzia; Atkinson, Lauren Z; Banaschewski, Tobias; Simonoff, Emily; Zuddas, Alessandro; Barbui, Corrado; Purgato, Marianna; Steinhausen, Hans-Christoph; Shokraneh, Farhad; Xia, Jun; Cipriani, Andrea; Coghill, David

2017-01-10

Attention-deficit/hyperactivity disorder (ADHD) is a major public health issue. Pharmacological treatments play an important role in the multimodal treatment of ADHD. Currently, there is a lack of up-to-date and comprehensive evidence on how available ADHD drugs compare and rank in terms of efficacy and tolerability, in children or adolescents as well as in adults. We will conduct a network meta-analysis (NMA), integrating direct and indirect comparisons from randomised controlled trials (RCTs), to rank pharmacological treatments for ADHD according to their efficacy and tolerability profiles. We will search a broad range of electronic databases, including PubMed, MEDLINE, EMBASE, PsycINFO, ERIC and Web of Science, with no date or language restrictions. We will also search for unpublished studies using international clinical trial registries and contacting relevant drug companies. We will identify and include available parallel-group, cross-over and cluster randomised trials that compare methylphenidate, dexmethylphenidate, amphetamine derivatives (including lisdexamfetamine), atomoxetine, clonidine, guanfacine, bupropion or modafinil (as oral therapy) either with each other or to placebo, in children, adolescents or adults with ADHD. Primary outcomes will be efficacy (indicated by reduction in severity of ADHD core symptoms measured on a standardised scale) and tolerability (the proportion of patients who left a study early due to side effects). Secondary outcomes will be global functioning, acceptability (proportion of patients who left the study early by any cause) and changes in blood pressure and body weight. NMA will be conducted in STATA within a frequentist framework. The quality of RCTs will be evaluated using the Cochrane risk of bias tool, and the quality of the evidence will be assessed using the GRADE approach. Subgroup and sensitivity analyses will be conducted to assess the robustness of the findings. No ethical issues are foreseen. Results from this

Development of a binary carrier system consisting polyethylene glycol 4000 - ethyl cellulose for ibuprofen solid dispersion

PubMed Central

Alagdar, Gada Sulaiman A.; Oo, May Kyaw; Sengupta, Pinaki; Mandal, Uttam Kumar; Jaffri, Julian Md.; Chatterjee, Bappaditya

2017-01-01

Background and Objective: One of the established strategies to improve solubility and dissolution rate of poorly water-soluble drugs is solid dispersion (SD). Polyethylene glycol (PEG) is used as common carrier despite its stability problem which may be overcome by the addition of hydrophobic polymer. The present research aimed to develop an SD formulation with ibuprofen, a poor water-soluble BCS Class II drug as active pharmaceutical ingredient (API) and PEG 4000-ethyl cellulose (EC) as binary carrier. Methods: Melt mixing SD method was employed using a ratio of API: binary carrier (1:3.5 w/w) (SDPE). Another SD was prepared using only PEG (SDP) as a carrier for comparative study. The developed formulation was evaluated using optical microscopy, scanning electron microscopy (SEM), determination of moisture content, differential scanning calorimetry (DSC), in vitro dissolution test, attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and flow properties. Results: SEM and DSC indicated the conversion of crystalline ibuprofen to fine partly amorphous solid dispersion, which was responsible for the increase in dissolution rate of SD than a physical mixture. The release characteristics within 1 h from the higher to the lower value were the SDPE> SDP> physical mixture. Flow property evaluation using the angle of repose showed no difference between SD and PM. However, by Carr index and Hausner ratio, the flow properties of SDPE was excellent. Conclusion: The SD formulation with the PEG 4000-EC carrier can be effective to enhance in vitro dissolution of ibuprofen immediate release dosage form. PMID:29184827

Exploiting Pharmacological Similarity to Identify Safety Concerns - Listen to What the Data Tells You.

PubMed

Muthas, Daniel; Boyer, Scott

2013-01-01

Whilst most new drugs are designed to act on a single target or a small number of targets, many do show broad pharmacological activity. In some cases this can be beneficial and necessary for efficacy and in others it can be detrimental, leading to increased safety liability. To probe off-target pharmacology most drug discovery programs include screening against a broad panel of targets that represent known troublesome pharmacology. Hits against any one of these targets can then be subjected to a risk assessment for potential safety problems in preclinical or clinical studies. In addition, the secondary pharmacology profile can also be thought of as an alternative description of the compound and as such can be used as a method for assessing 'similarity'. Consequently, inspection of the in vivo findings of pharmacological neighbors can give important insights into potential safety liabilities that are neither identified by pure chemical similarity searches nor by risk assessment on individual targets. Here we show that the pharmacological profile contains additional information as compared to chemical similarity, and also demonstrate how this can be used in the hazard assessment done during drug discovery and development. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pharmacology of pediatric resuscitation.

PubMed

Ushay, H M; Notterman, D A

1997-02-01

The resuscitation of children from cardiac arrest and shock remains a challenging goal. The pharmacologic principles underlying current recommendations for intervention in pediatric cardiac arrest have been reviewed. Current research efforts, points of controversy, and accepted practices that may not be most efficacious have been described. Epinephrine remains the most effective resuscitation adjunct. High-dose epinephrine is tolerated better in children than in adults, but its efficacy has not received full analysis. The preponderance of data continues to point toward the ineffectiveness and possible deleterious effects of overzealous sodium bicarbonate use. Calcium chloride is useful in the treatment of ionized hypocalcemia but may harm cells that have experienced asphyxial damage. Atropine is an effective agent for alleviating bradycardia induced by increased vagal tone, but because most bradycardia in children is caused by hypoxia, improved oxygenation is the intervention of choice. Adenosine is an effective and generally well-tolerated agent for the treatment of supraventricular tachycardia. Lidocaine is the drug of choice for ventricular dysrhythmias, and bretylium, still relatively unexplored, is in reserve. Many pediatricians use dopamine for shock in the postresuscitative period, but epinephrine is superior. Most animal research on cardiac arrest is based on models with ventricular fibrillation that probably are not reflective of cardiac arrest situations most often seen in pediatrics.

The design, synthesis and pharmacological characterization of novel β2-adrenoceptor antagonists

PubMed Central

Hothersall, J Daniel; Black, James; Caddick, Stephen; Vinter, Jeremy G; Tinker, Andrew; Baker, James R

2011-01-01

BACKGROUND AND PURPOSE Selective and potent antagonists for the β2-adrenoceptor are potentially interesting as experimental and clinical tools, and we sought to identify novel ligands with this pharmacology. EXPERIMENTAL APPROACH A range of pharmacological assays was used to assess potency, affinity, selectivity (β2-adrenoceptor vs. β1-adrenoceptor) and efficacy. KEY RESULTS Ten novel compounds were identified but none had as high affinity as the prototypical β2-adrenoceptor blocker ICI-118,551, although one of the novel compounds was more selective for β2-adrenoceptors. Most of the ligands were inverse agonists for β2-adrenoceptor-cAMP signalling, although one (5217377) was a partial agonist and another a neutral antagonist (7929193). None of the ligands were efficacious with regard to β2-adrenoceptor-β-arrestin signalling. The (2S,3S) enantiomers were identified as the most active, although unusually the racemates were the most selective for the β2-adrenoceptors. This was taken as evidence for some unusual enantiospecific behaviour. CONCLUSIONS AND IMPLICATIONS In terms of improving on the pharmacology of the ligand ICI-118,551, one of the compounds was more selective (racemic JB-175), while one was a neutral antagonist (7929193), although none had as high an affinity. The results substantiate the notion that β-blockers do more than simply inhibit receptor activation, and differences between the ligands could provide useful tools to investigate receptor biology. PMID:21323900

Pharmacological and clinical dilemmas of prescribing in co-morbid adult attention-deficit/hyperactivity disorder and addiction

PubMed Central

Pérez de los Cobos, José; Siñol, Núria; Pérez, Víctor; Trujols, Joan

2014-01-01

The present article reviews whether available efficacy and safety data support the pharmacological treatment of adult attention-deficit/hyperactivity disorder (ADHD) in patients with concurrent substance use disorders (SUD). Arguments for and against treating adult ADHD with active SUD are discussed. Findings from 19 large open studies and controlled clinical trials show that the use of atomoxetine or extended-release methylphenidate formulations, together with psychological therapy, yield promising though inconclusive results about short term efficacy of these drugs in the treatment of adult ADHD in patients with SUD and no other severe mental disorders. However, the efficacy of these drugs is scant or lacking for treating concurrent SUD. No serious safety issues have been associated with these drugs in patients with co-morbid SUD-ADHD, given their low risk of abuse and favourable side effect and drug–drug interaction profile. The decision to treat adult ADHD in the context of active SUD depends on various factors, some directly related to SUD-ADHD co-morbidity (e.g. degree of diagnostic uncertainty for ADHD) and other factors related to the clinical expertise of the medical staff and availability of adequate resources (e.g. the means to monitor compliance with pharmacological treatment). Our recommendation is that clinical decisions be individualized and based on a careful analysis of the advantages and disadvantages of pharmacological treatment for ADHD on a case-by-case basis in the context of active SUD. PMID:23216449

Thermolytic Degradation of Synthetic Cannabinoids: Chemical Exposures and Pharmacological Consequences.

PubMed

Thomas, Brian F; Lefever, Timothy W; Cortes, Ricardo A; Grabenauer, Megan; Kovach, Alexander L; Cox, Anderson O; Patel, Purvi R; Pollard, Gerald T; Marusich, Julie A; Kevin, Richard C; Gamage, Thomas F; Wiley, Jenny L

2017-04-01

Synthetic cannabinoids are manufactured clandestinely with little quality control and are distributed as herbal "spice" for smoking or as bulk compound for mixing with a solvent and inhalation via electronic vaporizers. Intoxication with synthetic cannabinoids has been associated with seizure, excited delirium, coma, kidney damage, and other disorders. The chemical alterations produced by heating these structurally novel compounds for consumption are largely unknown. Here, we show that heating synthetic cannabinoids containing tetramethylcyclopropyl-ring substituents produced thermal degradants with pharmacological activity that varied considerably from their parent compounds. Moreover, these degradants were formed under conditions simulating smoking. Some products of combustion retained high affinity at the cannabinoid 1 (CB 1 ) and CB 2 receptors, were more efficacious than (-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol (CP55,940) in stimulating CB 1 receptor-mediated guanosine 5'-O-(3-thiotriphosphate) (GTPγS) binding, and were potent in producing Δ 9 -tetrahydrocannabinol-like effects in laboratory animals, whereas other compounds had low affinity and efficacy and were devoid of cannabimimetic activity. Degradants that retained affinity and efficacy also substituted in drug discrimination tests for the prototypical synthetic cannabinoid 1-pentyl-3-(1-naphthoyl)indole (JWH-018), and are likely to produce psychotropic effects in humans. Hence, it is important to take into consideration the actual chemical exposures that occur during use of synthetic cannabinoid formulations to better comprehend the relationships between dose and effect. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Correlation of ibuprofen bioavailability with gastrointestinal transit by scintigraphic monitoring of /sup 171/Er-labeled sustained-release tablets

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

Parr, A.F.; Beihn, R.M.; Franz, R.M.

1987-12-01

External gamma scintigraphy was used to monitor the gastrointestinal (GI) transit of radiolabeled sustained-release tablets containing 800 mg ibuprofen in eight fasted healthy volunteers. Ibuprofen serum concentrations were determined from blood samples drawn sequentially over a 24-hr period. Serum concentrations and related parameters were correlated to the position of the dosage form in the GI tract from the scintiphotos. The sustained-release tablets were radiolabeled intact utilizing a neutron activation procedure, by incorporating 0.18% of /sup 170/Er2O3 (enriched to greater than 96% /sup 170/Er) into the bulk formulation. After manufacture of the final dosage forms, the tablets were irradiated in amore » neutron flux (4.4 x 10(13) n/cm2.sec) for 2 min, converting the stable /sup 170/Er to radioactive /sup 171/Er (t1/2 = 7.5 hr). Each tablet contained 50 microCi of /sup 171/Er at the time of administration. The scintigraphy studies suggested that the greatest proportion of ibuprofen was absorbed from this dosage form while the tablet was in the large bowel. The dosage forms eroded slowly in the small bowel and appeared to lose their integrity in the large bowel. In vitro studies showed only minimal effects of the neutron irradiation procedure on the dosage form performance.« less

Optimizing oncology therapeutics through quantitative translational and clinical pharmacology: challenges and opportunities.

PubMed

Venkatakrishnan, K; Friberg, L E; Ouellet, D; Mettetal, J T; Stein, A; Trocóniz, I F; Bruno, R; Mehrotra, N; Gobburu, J; Mould, D R

2015-01-01

Despite advances in biomedical research that have deepened our understanding of cancer hallmarks, resulting in the discovery and development of targeted therapies, the success rates of oncology drug development remain low. Opportunities remain for objective dose selection informed by exposure-response understanding to optimize the benefit-risk balance of novel therapies for cancer patients. This review article discusses the principles and applications of modeling and simulation approaches across the lifecycle of development of oncology therapeutics. Illustrative examples are used to convey the value gained from integration of quantitative clinical pharmacology strategies from the preclinical-translational phase through confirmatory clinical evaluation of efficacy and safety. © 2014 American Society for Clinical Pharmacology and Therapeutics.

Comparison of Pharmacological Potency and Safety of Glutamate Blocker IEM-1913 and Memantine.

PubMed

Gmiro, V E; Serdyuk, S E; Veselkina, O S

2015-11-01

Adamantane-containing glutamate blocker IEM-1913 (1-amino-4-(1-adamantane-amino)-butane dihydrochloride) equals to memantine in antiparkinsonian potency, but surpasses it in anticonvulsive, antidepressant, and analgesic activities. Moreover, its use is less toxic and safer. IEM-1913 produces significant pharmacological effects at a wide concentration diapason (0.03-1.00 mg/kg), while memantine is effective within a narrow range only (15-20 mg/kg). High pharmacological efficacy and low toxicity of IEM-1913 can be explained by the fact that in contrast to monocationic selective NMDA antagonist memantine, the dicationic glutamate blocker IEM-1913 produces a combined block of cerebral NMDA and AMPA receptors.

Development of ibuprofen-loaded nanostructured lipid carrier-based gels: characterization and investigation of in vitro and in vivo penetration through the skin

PubMed Central

Sütő, Blanka; Berkó, Szilvia; Kozma, Gábor; Kukovecz, Ákos; Budai-Szűcs, Mária; Erős, Gábor; Kemény, Lajos; Sztojkov-Ivanov, Anita; Gáspár, Róbert; Csányi, Erzsébet

2016-01-01

An ibuprofen-loaded nanostructured lipid carrier (IBU-NLC) was developed for enhanced skin penetration to improve the treatment of osteoarthritis and other musculoskeletal diseases. The mean particle size was 106 nm, with a spherical morphology, a smooth surface, and a zeta potential of −18.4 mV. X-ray diffraction studies revealed the amorphous state of the lipid matrix. Both Raman spectroscopy and Fourier transformation infrared analysis indicated no major shifts in the spectra of the formulations, which suggest rapid drug dissolution from the nanoparticles. The drug loading was 9.85%, and the entrapment efficiency was 98.51%. In vitro release of the NLC dispersion, in vitro permeation, and in vivo animal studies of IBU-NLC gel all confirmed that the permeation of IBU was significantly better than that of a reference after 6 hours. In conclusion, IBU-NLC gel is of great potential to enhance drug permeation through the skin and hence the efficacy of the treatment of chronic joint inflammation. PMID:27099487

Interventions for post-infectious irritable bowel syndrome: a systematic review of treatment efficacy.

PubMed

Torbicki, Emma; Oh, Justin; Mishra, Sharmistha; Page, Andrea V; Boggild, Andrea K

2015-01-01

Post-infectious irritable bowel syndrome (PI-IBS) due to traveler's diarrhea is the second most common illness seen in post-travel clinics, yet its optimal management remains unknown. We performed a systematic review to evaluate treatment efficacy in PI-IBS. We searched Medline, EMBASE, LILACS, CINAHL, CAB abstracts, and the Cochrane Library to February 3, 2014 for intervention studies of the pharmacologic and non-pharmacologic management of PI-IBS and examined the evidence according to a modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) scale. Of 336 records, 9 studies were included. Eight studies of pharmacologic interventions examined 5 agents (mesalazine or mesalamine, ondansetron, prednisolone, cholestyramine, and metronidazole). One study examined the non-pharmacologic intervention of different infant nutritional formulas following acute gastroenteritis. The quality of the evidence to date was low, with small sample size (fewer than 50 participants) and short duration of follow-up. Overall, the efficacy of pharmacological treatment ranged from no benefit (ondansetron and prednisolone) to moderately beneficial (cholestyramine and metronidazole). The evidence for mesalazine was equivocal: one study showed benefit, two others showed none. Heterogeneity in outcome measures and low strength of evidence preclude recommendations on the optimal management of PI-IBS by a specific agent. More comparative intervention research into PI-IBS treatment is needed for consistent best practice in PI-IBS management. Clinicians may elect to pursue therapeutic trials of mesalazine, cholestyramine, or metronidazole in individual patients, but should be aware that data supporting the efficacy of these agents is limited.

Oral paracetamol versus oral ibuprofen for closure of haemodynamically significant patent ductus arteriosus in preterm neonates (<32 weeks): a blinded, randomised, active-controlled, non-inferiority trial

PubMed Central

Kumar, Ashutosh; Sundaram, Venkataseshan; Yadav, Rahul; Oleti, Tejo Pratap; Murki, Srinivas; Krishna, Arun; Sundaram, Mangalabharathi; Saini, Shiv Sajan; Dutta, Sourabh

2017-01-01

Introduction Haemodynamically significant patent ductus arteriosus (hsPDA) is a common cause of mortality and morbidity in preterm infants. Existing medical therapies with ibuprofen or indomethacin have multiple adverse effects. Hence, an alternative drug like paracetamol given through oral route with less side effects need to be tested in an appropriate study design with least risk of bias to arrive at a conclusion. Methods and analysis Multisite, randomised, active-controlled, non-inferiority design. The primary objective is to study the efficacy of oral paracetamol for closure of hsPDA in comparison to oral ibuprofen in preterm neonates of <32 weeks’ gestation. Randomisation web-based and allocation concealment would be done; the treating team, investigators, outcome assessors and laboratory personnel would be blinded from the intervention. Echocardiography images would be coded for independent review. Closure of PDA by the end of last dose of study drug or earlier would be the study endpoint. A sample size of 196 neonates would be enrolled with a non-inferiority margin of 15%. Both intention-to-treat and per-protocol analysis will be done to assess the effect of contamination and protocol violations in the primary outcome. Ethics and dissemination The trial would follow international code of ethics for clinical trial. The trial protocol was approved by the Institute Ethics Committee of all three centres. All serious adverse events would be reported in detail to the Institute Ethics Committee. A written informed consent would be obtained from one of the parents. No plan has been made for dissemination. Trial registration number CTRI/2014/08/004805. PMID:29637155

Psychosocial and pharmacological management of pain in pediatric sickle cell disease.

PubMed

Hildenbrand, Aimee K; Nicholls, Elizabeth G; Daly, Brian P; Marsac, Meghan L; Tarazi, Reem; Deepti, Raybagkar

2014-03-01

For children with sickle cell disease (SCD), pain is associated with significant current and future morbidity and mortality. Unfortunately, few evidence-based guidelines exist for the management of pain episodes in children with SCD. To inform empirically based treatment strategies for pain management in pediatric SCD, this review integrates and evaluates the extant literature on psychosocial and pharmacological approaches to the management of pain. Findings reveal a paucity of rigorous investigations of psychosocial and pharmacological pain management interventions in children with SCD. Psychosocial interventions included were primarily cognitive-behavioral in nature, whereas pharmacological approaches targeted non-opioid analgesics (ie, nonsteroidal anti-inflammatory drugs and corticosteroids) and opioid medications (ie, morphine and oxycodone). However, to date there is not a "gold standard" for pain management among children with SCD. Because psychosocial and physiological processes each play a role in the etiology and experience of pain, effective pain management requires multidimensional, comprehensive treatment approaches. Considering the significant impact of pain on functional outcomes and quality of life among children with SCD, additional clinical trials are warranted to ensure that interventions are safe and efficacious.

Ibuprofen therapy resulted in significantly decreased tissue bacillary loads and increased survival in a new murine experimental model of active tuberculosis.

PubMed

Vilaplana, Cristina; Marzo, Elena; Tapia, Gustavo; Diaz, Jorge; Garcia, Vanesa; Cardona, Pere-Joan

2013-07-15

C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment.

And to end on a poetic note: Galen’s authorial strategies in the pharmacological books

PubMed Central

Totelin, Laurence M.V.

2012-01-01

This paper examines the authorial strategies deployed by Galen in his two main pharmacological treatises devoted to compound remedies: Composition of Medicines according to Types and Composition of Medicines according to Places. Some of Galen’s methods of self assertion (use of the first person; writing of prefaces) are conventional. Others have not received much attention from scholars. Thus, here, I examine Galen’s borrowing of his sources’ ‘I’; his use of the phrase ‘in these words’; and his recourse to Damocrates’ verse to conclude pharmacological books. I argue that Galen’s authorial persona is very different from that of the modern author as defined by Roland Barthes. Galen imitates and impersonates his pharmacological sources. This re-enactment becomes a way to gain experience (peira) of remedies and guarantees their efficacy.

Bone Loss from High Repetitive High Force Loading is Prevented by Ibuprofen Treatment

PubMed Central

Jain, Nisha X.; Barr-Gillespie, Ann E.; Clark, Brian D.; Kietrys, David M.; Wade, Christine K.; Litvin, Judith; Popoff, Steven N.; Barbe, Mary F.

2014-01-01

We examined roles of loading and inflammation on forearm bones in a rat model of upper extremity overuse. Trabecular structure in distal radius and ulna was examined in three groups of young adult rats: 1) 5% food-restricted that underwent an initial training period of 10 min/day for 5 weeks to learn the repetitive task (TRHF); 2) rats that underwent the same training before performing a high repetition high force task, 2 hours/day for 12 weeks (HRHF); and 3) food-restricted only (FRC). Subsets were treated with oral ibuprofen (IBU). TRHF rats had increased trabecular bone volume and numbers, osteoblasts, and serum osteocalcin, indicative of bone adaptation. HRHF rats had constant muscle pulling forces, showed limited signs of bone adaptation, but many signs of bone resorption, including decreased trabecular bone volume and bone mineral density, increased osteoclasts and bone inflammatory cytokines, and reduced median nerve conduction velocity (15%). HRHF+IBU rats showed no trabecular resorptive changes, no increased osteoclasts or bone inflammatory cytokines, no nerve inflammation, preserved nerve conduction, and increased muscle voluntary pulling forces. Ibuprofen treatment preserved trabecular bone quality by reducing osteoclasts and bone inflammatory cytokines, and improving muscle pulling forces on bones as a result of reduced nerve inflammation. PMID:24583543

Sunitinib-ibuprofen drug interaction affects the pharmacokinetics and tissue distribution of sunitinib to brain, liver, and kidney in male and female mice differently.

PubMed

Lau, Christine Li Ling; Chan, Sook Tyng; Selvaratanam, Manimegahlai; Khoo, Hui Wen; Lim, Adeline Yi Ling; Modamio, Pilar; Mariño, Eduardo L; Segarra, Ignacio

2015-08-01

Tyrosine kinase inhibitor sunitinib (used in GIST, advanced RCC, and pancreatic neuroendocrine tumors) undergoes CYP3A4 metabolism and is an ABCB1B and ABCG2 efflux transporters substrate. We assessed the pharmacokinetic interaction with ibuprofen (an NSAID used by patients with cancer) in Balb/c male and female mice. Mice (study group) were coadministered (30 min apart) 30 mg/kg of ibuprofen and 60 mg/kg of sunitinib PO and compared with the control groups, which received sunitinib alone (60 mg/kg, PO). Sunitinib concentration in plasma, brain, kidney, and liver was measured by HPLC as scheduled and noncompartmental pharmacokinetic parameters estimated. In female control mice, sunitinib AUC0→∞ decreased in plasma (P < 0.05), was higher in liver and brain (P < 0.001), and lower in kidney (P < 0.001) vs. male control mice. After ibuprofen coadministration, female mice showed lower AUC0→∞ in plasma (P < 0.01), brain, liver, and kidney (all P < 0.001). However, in male mice, AUC0→∞ remained unchanged in plasma, increased in liver and kidney, and decreased in brain (all P < 0.001). The tissue-to-plasma AUC0→∞ ratio was similar between male and female control mice, but changed after ibuprofen coadministration: Male mice showed 1.6-fold higher liver-to-plasma ratio (P < 0.001) while remained unchanged in female mice and in kidney (male and female mice) but decreased 55% in brain (P < 0.05). The tissue-to-plasma partial AUC ratio, the drug tissue targeting index, and the tissue-plasma hysteresis-like plots also showed sex-based ibuprofen-sunitinib drug interaction differences. The results illustrate the relevance of this DDI on sunitinib pharmacokinetics and tissue uptake. These may be due to gender-based P450 and efflux/transporters differences. © 2015 Société Française de Pharmacologie et de Thérapeutique.

Efficacy and safety of tamsulosin as a medical expulsive therapy for stones in children.

PubMed

Aldaqadossi, Hussein A; Shaker, Hossam; Saifelnasr, Mohammed; Gaber, Mohammed

2015-06-01

To evaluate the efficacy of tamsulosin for promoting ureteric stone expulsion in children, based on the confirmed efficacy of tamsulosin as a medical expulsive therapy in adults. From February 2010 to July 2013, 67 children presenting with a distal ureteric stone of <1 cm as assessed on unenhanced computed tomography were included in the study. The patients were randomised into two groups, with group 1 (33 patients) receiving tamsulosin 0.4 mg and ibuprofen, and group 2 (34) receiving ibuprofen only. They were followed up for 4 weeks. Endoscopic intervention was indicated for patients with uncontrolled pain, recurrent urinary tract infection, hypersensitivity to tamsulosin and failure of stone passage after 4 weeks of conservative treatment. Sixty-three patients completed the study. There were no statistically significant differences between the groups in patient age, body weight and stone size, the mean (SD) of which was 6.52 (1.8) mm in group 1 vs. 6.47 (1.79) mm in group 2 (P = 0.9). The mean (SD) time to stone expulsion in group 1 was 7.7 (1.9) days, vs. 18 (1.73) days in group 2 (P < 0.001). The analgesic requirement (mean number of ketorolac injections) in group 1 was significantly less than in group 2, at 0.55 (0.8) vs. 1.8 (1.6) (P < 0.001). The stone-free rate was 87% in group 1 and 63% in group 2 (P = 0.025). Tamsulosin used as a medical expulsive therapy for children with ureteric stones is safe and effective, as it facilitates spontaneous expulsion of the stone.

The Evaluation of Benefit of Newly Prepared Reversible Inhibitors of Acetylcholinesterase and Commonly Used Pyridostigmine as Pharmacological Pretreatment of Soman-Poisoned Mice.

PubMed

Kassa, Jiří; Korábečný, Jan; Nepovimová, Eugenie

The ability of four newly prepared reversible inhibitors of acetylcholinesterase (6-chlorotacrine, 7-phenoxytacrine, compounds 1 and 2) and currently used carbamate pyridostigmine to increase the resistance of mice against soman and the efficacy of antidotal treatment of soman-poisoned mice was evaluated. The evaluation of the effect of pharmacological pretreatment is based on the identification of changes of soman-induced toxicity that was evaluated by the assessment of its LD50 value and its 95% confidence limit using probitlogarithmical analysis of death occurring within 24 h after administration of soman. 6-chlorotacrine was only able to markedly protect mice against acute toxicity of soman. In addition, the pharmacological pretreatment with 6-chlorotacrine or compound 2 was able to increase the efficacy of antidotal treatment (the oxime HI-6 in combination with atropine) of soman-poisoned mice. The other newly prepared reversible inhibitors of acetylcholinesterase (7-phenoxytacrine, compound 1) as well as commonly used pyridostigmine did not influence the efficacy of antidotal treatment. These findings demonstrate that pharmacological pretreatment of somanpoisoned mice can be promising and useful in the case of administration of 6-chlorotacrine and partly compound 2.

Non-pharmacological cognitive intervention for aging and dementia: Current perspectives

PubMed Central

Alves, Jorge; Magalhães, Rosana; Machado, Álvaro; Gonçalves, Óscar F; Sampaio, Adriana; Petrosyan, Agavni

2013-01-01

In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting healthy cognition has become a priority and a necessity for minimizing and preventing individual and societal burdens associated with cognitive dysfunctions in the elderly. The general awareness concerning the efficacy of preventive (e.g., lifestyles) and palliative treatment strategies of cognitive impairments, related to either healthy or unhealthy trajectories in cognitive aging, is continuously rising. There are several therapeutic strategies which can be broadly classified as either pharmacological or non-pharmacological/psychosocial. In face of the modest evidence for success of pharmacological treatments, especially for dementia related impairments, psychosocial interventions are progressively considered as a complementary treatment. Despite the relative spread of psychosocial interventions in clinical settings, research in this area is rather scarce with evidence for success of these therapies remaining controversial. In this work we provide an evidence based perspective on cognitive intervention(s) for healthy aging, pre-dementia (mild cognitive impairment), and dementia populations. Current evidence and future directions for improving cognitive functions in the elderly are discussed as well. PMID:24340275

Enantiomeric analysis of overlapped chromatographic profiles in the presence of interferences. Determination of ibuprofen in a pharmaceutical formulation containing homatropine.

PubMed

Padró, J M; Osorio-Grisales, J; Arancibia, J A; Olivieri, A C; Castells, C B

2016-10-07

In this work, we studied the combination of chemometric methods with chromatographic separations as a strategy applied to the analysis of enantiomers when complete enantioseparation is difficult or requires long analysis times and, in addition, the target signals have interference from the matrix. We present the determination of ibuprofen enantiomers in pharmaceutical formulations containing homatropine as interference by chiral HPLC-DAD detection in combination with partial least-squares algorithms. The method has been applied to samples containing enantiomeric ratios from 95:5 to 99.5:0.5 and coelution of interferents. The results were validated using univariate calibration and without homatropine. Relative error of the method was less than 4.0%, for both enantiomers. Limits of detection (LOD) and quantification (LOQ) for (S)-(+)-ibuprofen were 4.96×10 -10 and 1.50×10 -9 mol, respectively. LOD and LOQ for the R-(-)-ibuprofen were LOD=1.60×10 -11 mol and LOQ=4.85×10 -11 mol, respectively. Finally, the chemometric method was applied to the determination of enantiomeric purity of commercial pharmaceuticals. The ultimate goal of this research was the development of rapid, reliable, and robust methods for assessing enantiomeric purity by conventional diode array detector assisted by chemometric tools. Copyright © 2016 Elsevier B.V. All rights reserved.

Lung Function Measurements in Rodents in Safety Pharmacology Studies

PubMed Central

Hoymann, Heinz Gerd

2012-01-01

The ICH guideline S7A requires safety pharmacology tests including measurements of pulmonary function. In the first step – as part of the “core battery” – lung function tests in conscious animals are requested. If potential adverse effects raise concern for human safety, these should be explored in a second step as a “follow-up study”. For these two stages of safety pharmacology testing, both non-invasive and invasive techniques are needed which should be as precise and reliable as possible. A short overview of typical in vivo measurement techniques is given, their advantages and disadvantages are discussed and out of these the non-invasive head-out body plethysmography and the invasive but repeatable body plethysmography in orotracheally intubated rodents are presented in detail. For validation purposes the changes in the respective parameters such as tidal midexpiratory flow (EF50) or lung resistance have been recorded in the same animals in typical bronchoconstriction models and compared. In addition, the technique of head-out body plethysmography has been shown to be useful to measure lung function in juvenile rats starting from day two of age. This allows safety pharmacology testing and toxicological studies in juvenile animals as a model for the young developing organism as requested by the regulatory authorities (e.g., EMEA Guideline 1/2008). It is concluded that both invasive and non-invasive pulmonary function tests are capable of detecting effects and alterations on the respiratory system with different selectivity and area of operation. The use of both techniques in a large number of studies in mice and rats in the last years have demonstrated that they provide useful and reliable information on pulmonary mechanics in safety pharmacology and toxicology testing, in investigations of respiratory disorders, and in pharmacological efficacy studies. PMID:22973226

Swiss University Students' Attitudes toward Pharmacological Cognitive Enhancement.

PubMed

Maier, Larissa J; Liakoni, Evangelia; Schildmann, Jan; Schaub, Michael P; Liechti, Matthias E

2015-01-01

Pharmacological cognitive enhancement (PCE) refers to the nonmedical use of prescription or recreational drugs to enhance cognitive performance. Several concerns about PCE have been raised in the public. The aim of the present study was to investigate students' attitudes toward PCE. Students at three Swiss universities were invited by e-mail to participate in a web-based survey. Of the 29,282 students who were contacted, 3,056 participated. Of these students, 22% indicated that they had used prescription drugs (12%) or recreational substances including alcohol (14%) at least once for PCE. The use of prescription drugs or recreational substances including alcohol prior to the last exam was reported by 16%. Users of pharmacological cognitive enhancers were more likely to consider PCE fair (24%) compared with nonusers (11%). Only a minority of the participants agreed with the nonmedical use of prescription drugs by fellow students when assuming weak (7%) or hypothetically strong efficacy and availability to everyone (14%). Two-thirds (68%) considered performance that is obtained with PCE less worthy of recognition. Additionally, 80% disagreed that PCE is acceptable in a competitive environment. More than half (64%) agreed that PCE in academia is similar to doping in sports. Nearly half (48%) claimed that unregulated access to pharmacological cognitive enhancers increases the pressure to engage in PCE and educational inequality (55%). In conclusion, Swiss students' main concerns regarding PCE were related to coercion and fairness. As expected, these concerns were more prevalent among nonusers than among users of pharmacological cognitive enhancers. More balanced information on PCE should be shared with students, and future monitoring of PCE is recommended.

Swiss University Students’ Attitudes toward Pharmacological Cognitive Enhancement

PubMed Central

Maier, Larissa J.; Liakoni, Evangelia; Schildmann, Jan; Schaub, Michael P.; Liechti, Matthias E.

2015-01-01

Pharmacological cognitive enhancement (PCE) refers to the nonmedical use of prescription or recreational drugs to enhance cognitive performance. Several concerns about PCE have been raised in the public. The aim of the present study was to investigate students’ attitudes toward PCE. Students at three Swiss universities were invited by e-mail to participate in a web-based survey. Of the 29,282 students who were contacted, 3,056 participated. Of these students, 22% indicated that they had used prescription drugs (12%) or recreational substances including alcohol (14%) at least once for PCE. The use of prescription drugs or recreational substances including alcohol prior to the last exam was reported by 16%. Users of pharmacological cognitive enhancers were more likely to consider PCE fair (24%) compared with nonusers (11%). Only a minority of the participants agreed with the nonmedical use of prescription drugs by fellow students when assuming weak (7%) or hypothetically strong efficacy and availability to everyone (14%). Two-thirds (68%) considered performance that is obtained with PCE less worthy of recognition. Additionally, 80% disagreed that PCE is acceptable in a competitive environment. More than half (64%) agreed that PCE in academia is similar to doping in sports. Nearly half (48%) claimed that unregulated access to pharmacological cognitive enhancers increases the pressure to engage in PCE and educational inequality (55%). In conclusion, Swiss students’ main concerns regarding PCE were related to coercion and fairness. As expected, these concerns were more prevalent among nonusers than among users of pharmacological cognitive enhancers. More balanced information on PCE should be shared with students, and future monitoring of PCE is recommended. PMID:26657300

Pharmacological prevention of rocuronium-induced injection pain or withdrawal movements: a meta-analysis.

PubMed

Kwak, Hyun Jeong; Kim, Ji Young; Kim, Yong Beom; Min, Sang Kee; Moon, Bong Ki; Kim, Jong Yeop

2013-10-01

Rocuronium is reported to be associated with injection pain or withdrawal movement (IPWM). This meta-analysis assessed the efficacy of different pharmacological treatments used to decrease the incidence of the rocuronium-induced IPWM. We searched the Cochrane Library, Embase and PubMed for randomized controlled trials comparing a pharmacological drug with a placebo to prevent the rocuronium-induced IPWM and found 37 studies with 5,595 patients. Overall incidence of rocuronium-induced IPWM was 74%. Pretreatment with opioids [risk ratio (RR) 0.16; 95% confidence interval (95% CI) 0.09-0.29], lidocaine (0.47; 0.35-0.64), and ketamine (0.41; 0.22-0.77) were effective in decreasing IPWM. Lidocaine pretreatment with venous occlusion (0.40; 0.32-0.49) and opioids pretreatment with venous occlusion (0.77; 0.61-0.96) were also effective. Mixing sodium bicarbonate (NaHCO3) with rocuronium (0.15; 0.06-0.34) was also efficacious in reducing IPWM. Indirect comparison shows that the RR of NaHCO3 admixture and pretreatment with opioids were lower than that of the other four interventions (pretreatments of ketamine or lidocaine, and lidocaine or opioids with venous occlusion). This meta-analysis suggests that opioids, lidocaine, ketamine, and NaHCO3 are effective in decreasing rocuronium-induced IPWM. Considering the efficacy and convenience, pretreatment with opioids without venous occlusion is recommended for reducing rocuronium-induced IPWM.

Pharmacologic interventions in aging hair

PubMed Central

Trüeb, Ralph M

2006-01-01

The appearance of hair plays an important role in people’s overall physical appearance and self-perception. With today’s increasing life-expectations, the desire to look youthful plays a bigger role than ever. The hair care industry has become aware of this and is delivering active products directed towards meeting this consumer demand. The discovery of pharmacological targets and the development of safe and effective drugs also indicate strategies of the drug industry for maintenance of healthy and beautiful hair. Hair aging comprises weathering of the hair shaft, decrease of melanocyte function, and decrease in hair production. The scalp is subject to intrinsic and extrinsic aging. Intrinsic factors are related to individual genetic and epigenetic mechanisms with interindividual variation: prototypes are familial premature graying, and androgenetic alopecia. Currently available pharmacologic treatment modalities with proven efficacy for treatment of androgenetic alopecia are topical minoxidil and oral finasteride. Extrinsic factors include ultraviolet radiation and air pollution. Experimental evidence supports the hypothesis that oxidative stress also plays a role in hair aging. Topical anti-aging compounds include photoprotectors and antioxidants. In the absence of another way to reverse hair graying, hair colorants remain the mainstay of recovering lost hair color. Topical liposome targeting for melanins, genes, and proteins selectively to hair follicles are currently under investigation. PMID:18044109

Current Approaches and New Developments in the Pharmacological Management of Tourette Syndrome.

PubMed

Quezada, Julio; Coffman, Keith A

2018-01-01

Tourette syndrome (TS) is a neurodevelopmental disorder of unknown etiology characterized by spontaneous, involuntary movements and vocalizations called tics. Once thought to be rare, TS affects 0.3-1% of the population. Tics can cause physical discomfort, emotional distress, social difficulties, and can interfere with education and desired activities. The pharmacologic treatment of TS is particularly challenging, as currently the genetics, neurophysiology, and neuropathology of this disorder are still largely unknown. However, clinical experience gained from treating TS has helped us better understand its pathogenesis and, as a result, derive treatment options. The strongest data exist for the antipsychotic agents, both typical and atypical, although their use is often limited in children and adolescents due to their side-effect profiles. There are agents in a variety of other pharmacologic categories that have evidence for the treatment of TS and whose side-effect profiles are more tolerable than the antipsychotics; these include clonidine, guanfacine, baclofen, topiramate, botulinum toxin A, tetrabenazine, and deutetrabenazine. A number of new agents are being developed and tested as potential treatments for TS. These include valbenazine, delta-9-tetrahydrocannabidiol, and ecopipam. Additionally, there are agents with insufficient data for efficacy, as well as agents that have been shown to be ineffective. Those without sufficient data for efficacy include clonazepam, ningdong granule, 5-ling granule, omega-3 fatty acids, and n-acetylcysteine. The agents that have been shown to be ineffective include pramipexole and metoclopramide. We will review all of the established pharmacologic treatments, and discuss those presently in development.

In vitro permeation and in vivo anti-inflammatory and analgesic properties of nanoscaled emulsions containing ibuprofen for topical delivery

PubMed Central

Abdullah, Ghassan Z; Abdulkarim, Muthanna F; Salman, Ibrahim M; Ameer, Omar Z; Yam, Mun F; Mutee, Ahmed F; Chitneni, Mallikarjun; Mahdi, Elrashid S; Basri, Mahiran; Sattar, Munavvar A; Noor, Azmin M

2011-01-01

Introduction: As a topical delivery system, a nanoscaled emulsion is considered a good carrier of several active ingredients that convey several side effects upon oral administration, such as nonsteroidal anti-inflammatory drugs (NSAIDs). Objective: We investigated the in vitro permeation properties and the in vivo pharmacodynamic activities of different nanoscaled emulsions containing ibuprofen, an NSAID, as an active ingredient and newly synthesized palm olein esters (POEs) as the oil phase. Methodology: A ratio of 25:37:38 of oil phase:aqueous phase:surfactant was used, and different additives were used for the production of a range of nanoscaled emulsions. Carbopol® 940 dispersion neutralized by triethanolamine was employed as a rheology modifier. In some circumstances, menthol and limonene were employed at different concentrations as permeation promoters. All formulae were assessed in vitro using Franz diffusion cell fitted with full-thickness rat skin. This was followed by in vivo evaluation of the anti-inflammatory and analgesic activities of the promising formulae and comparison of the effects with that of the commercially available gel. Results and discussion: Among all other formulae, formula G40 (Carbopol® 940-free formula) had a superior ability in transferring ibuprofen topically compared with the reference. Carbopol® 940 significantly decreased the amount of drug transferred from formula G41 through the skin as a result of swelling, gel formation, and reduction in drug thermodynamic activity. Nonetheless, the addition of 10% w/w of menthol and limonene successfully overcame this drawback since, relative to the reference, higher amount of ibuprofen was transferred through the skin. By contrast, these results were relatively comparable to that of formula G40. Pharmacodynamically, the G40, G45, and G47 formulae exhibited the highest anti-inflammatory and analgesic effects compared with other formulae. Conclusion: The ingredients and the physical

Principles of Safety Pharmacology

PubMed Central

Pugsley, M K; Authier, S; Curtis, M J

2008-01-01

Safety Pharmacology is a rapidly developing discipline that uses the basic principles of pharmacology in a regulatory-driven process to generate data to inform risk/benefit assessment. The aim of Safety Pharmacology is to characterize the pharmacodynamic/pharmacokinetic (PK/PD) relationship of a drug's adverse effects using continuously evolving methodology. Unlike toxicology, Safety Pharmacology includes within its remit a regulatory requirement to predict the risk of rare lethal events. This gives Safety Pharmacology its unique character. The key issues for Safety Pharmacology are detection of an adverse effect liability, projection of the data into safety margin calculation and finally clinical safety monitoring. This article sets out to explain the drivers for Safety Pharmacology so that the wider pharmacology community is better placed to understand the discipline. It concludes with a summary of principles that may help inform future resolution of unmet needs (especially establishing model validation for accurate risk assessment). Subsequent articles in this issue of the journal address specific aspects of Safety Pharmacology to explore the issues of model choice, the burden of proof and to highlight areas of intensive activity (such as testing for drug-induced rare event liability, and the challenge of testing the safety of so-called biologics (antibodies, gene therapy and so on.). PMID:18604233

Advancing pharmacometrics and systems pharmacology.

PubMed

Waldman, S A; Terzic, A

2012-11-01

Pharmacometrics and systems pharmacology are emerging as principal quantitative sciences within drug development and experimental therapeutics. In recognition of the importance of pharmacometrics and systems pharmacology to the discipline of clinical pharmacology, the American Society for Clinical Pharmacology and Therapeutics (ASCPT), in collaboration with Nature Publishing Group and Clinical Pharmacology & Therapeutics, has established CPT: Pharmacometrics & Systems Pharmacology to inform the field and shape the discipline.

Comparison of ibuprofen release from minitablets and capsules containing ibuprofen: β-cyclodextrin complex.

PubMed

Salústio, P J; Cabral-Marques, H M; Costa, P C; Pinto, J F

2011-05-01

Mixtures containing ibuprofen (IB) complexed with β-cyclodextrin (βCD) obtained by two complexation methods [suspension/solution (with water removed by air stream, spray- and freeze-drying) and kneading technique] were processed into pharmaceutical dosage forms (minitablets and capsules). Powders (IB, βCD and IBβCD) were characterized for moisture content, densities (true and bulk), angle of repose and Carr's index, X-ray and NMR. From physical mixtures and IBβCD complexes without other excipients were prepared 2.5-mm-diameter minitablets and capsules. Minitablets were characterized for the energy of compaction, tensile strength, friability, density and IB release (at pH 1.0 and 7.2), whereby capsules were characterized for IB release. The results from the release of IB were analyzed using different parameters, namely, the similarity factor (f(2)), the dissolution efficiency (DE) and the amounts released at a certain time (30, 60 and 180 min) and compared statistically (α=0.05). The release of IB from the minitablets showed no dependency on the amount of water used in the formation of the complexes. Differences were due to the compaction force used or the presence of a shell for the capsules. The differences observed were mostly due to the characteristics of the particles (dependent on the method considered on the formation of the complexes) and neither to the dosage form nor to the complex of the IB. Copyright © 2011 Elsevier B.V. All rights reserved.

Behavioral and pharmacologic therapies for obesity

PubMed Central

Vetter, Marion L.; Faulconbridge, Lucy F.; Webb, Victoria L.; Wadden, Thomas A.

2011-01-01

This article reviews novel developments in the behavioral and pharmacologic treatment of obesity and explores the potential contribution of genomics research to weight control. A comprehensive program of lifestyle modification, comprised of diet, physical activity and behavior therapy, induces a mean loss of 7–10% of initial weight in individuals with obesity. Two trials demonstrated that weight loss of this magnitude, combined with increased physical activity, substantially reduced the risk of developing type 2 diabetes mellitus in individuals with impaired glucose tolerance. A third trial is now investigating whether a lifestyle intervention will reduce cardiovascular morbidity and mortality in overweight individuals who already have diabetes mellitus. Pharmacotherapy is recommended, in some patients, as an adjunct to lifestyle modification. Two medications—orlistat and sibutramine—are currently approved in the US for long-term weight loss. Both are efficacious when combined with lifestyle modification, although health concerns have been raised about the use of sibutramine. Several novel combination therapies, which target multiple hypothalamic pathways that regulate appetite and body weight, are currently under investigation. Genomic studies provide further evidence for the role of these pathways in the regulation of body weight. Identification of new genes controlling satiety and energy expenditure may yield valuable clues for the development of novel pharmacologic treatments. PMID:20680034

The Effects of Oral Ibuprofen on Medicinal Closure of Patent Ductus Arteriosus in Full-Term Neonates in the Second Postnatal Week

PubMed Central

Alipour, Mohammad Reza; Mozaffari Shamsi, Mansooreh; Namayandeh, Seyedeh Mahdieh; Pezeshkpour, Zohreh; Rezaeipour, Fatemeh; Sarebanhassanabadi, Mohammadtaghi

2016-01-01

Background The arterial ductus is a major communicative pathway which is naturally patent in the fetus, connecting the body of the major pulmonary artery to the descending aorta. Although usually closing on its own, the patent ductus arteriosus (PDA) may remain open in the second postnatal week due to a lack of prompt diagnosis in the initial days of life or an absence of prompt treatment. Objectives To prevent the untoward sequelae of patency of the ductus arteriosus, and to avoid invasive surgery at higher ages, the researchers in the present study embarked on determining the effects of oral ibuprofen during the second postnatal week on newborns with patent ductus arteriosus. Patients and Methods In this study, 70 neonates aged eight to 14 days, presenting at Khatam-al-Anbia clinic and the NICU ward of Shahid Sadoughi hospital in Yazd, Iran, who were diagnosed with PDA through auscultation of heart murmurs and echocardiography, were randomly assigned to two groups. The experimental group received oral ibuprofen of 10 mg/kg in day 1, 5 mg/kg in day 2, and 5 mg/kg in day 3 administered by their parents. The control group did not receive any drug. Parents were informed of the potential drug complications and side effects and asked to report them to the researchers if any occurred. Results After intervention, the patent ductus arteriosus was closed in 62.9% of the neonates in the experimental group (35 newborns) who received oral ibuprofen, while it was closed in 54.3% of the control neonates (35 newborns) who did not receive any drug (P = 0.628). No complications were observed in either of the neonatal groups. Conclusions Our findings showed that administration of oral ibuprofen had no significant effect on the medicinal closure of PDA in full-term neonates during the second postnatal week. PMID:27729962

The Effects of Oral Ibuprofen on Medicinal Closure of Patent Ductus Arteriosus in Full-Term Neonates in the Second Postnatal Week.

PubMed

Alipour, Mohammad Reza; Mozaffari Shamsi, Mansooreh; Namayandeh, Seyedeh Mahdieh; Pezeshkpour, Zohreh; Rezaeipour, Fatemeh; Sarebanhassanabadi, Mohammadtaghi

2016-08-01

The arterial ductus is a major communicative pathway which is naturally patent in the fetus, connecting the body of the major pulmonary artery to the descending aorta. Although usually closing on its own, the patent ductus arteriosus (PDA) may remain open in the second postnatal week due to a lack of prompt diagnosis in the initial days of life or an absence of prompt treatment. To prevent the untoward sequelae of patency of the ductus arteriosus, and to avoid invasive surgery at higher ages, the researchers in the present study embarked on determining the effects of oral ibuprofen during the second postnatal week on newborns with patent ductus arteriosus. In this study, 70 neonates aged eight to 14 days, presenting at Khatam-al-Anbia clinic and the NICU ward of Shahid Sadoughi hospital in Yazd, Iran, who were diagnosed with PDA through auscultation of heart murmurs and echocardiography, were randomly assigned to two groups. The experimental group received oral ibuprofen of 10 mg/kg in day 1, 5 mg/kg in day 2, and 5 mg/kg in day 3 administered by their parents. The control group did not receive any drug. Parents were informed of the potential drug complications and side effects and asked to report them to the researchers if any occurred. After intervention, the patent ductus arteriosus was closed in 62.9% of the neonates in the experimental group (35 newborns) who received oral ibuprofen, while it was closed in 54.3% of the control neonates (35 newborns) who did not receive any drug (P = 0.628). No complications were observed in either of the neonatal groups. Our findings showed that administration of oral ibuprofen had no significant effect on the medicinal closure of PDA in full-term neonates during the second postnatal week.

Preclinical studies identify novel targeted pharmacological strategies for treatment of human malignant pleural mesothelioma.

PubMed

Favoni, Roberto E; Daga, Antonio; Malatesta, Paolo; Florio, Tullio

2012-05-01

The incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up-to-date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum derivatives and pemetrexed or raltitrexed, as preferred first-line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy-resistant disease. Over these foundations, several promising studies are ongoing at preclinical level and novel molecules are currently under evaluation as well. Yet, established tumour cell lines, used for decades to investigate the efficacy of anticancer agents, although still the main source of drug efficacy studies, after long-term cultures tend to biologically diverge from the original tumour, limiting the predictive potential of in vivo efficacy. Cancer stem cells (CSCs), a subpopulation of malignant cells capable of self-renewal and multilineage differentiation, are believed to play an essential role in cancer initiation, growth, metastasization and relapse, being responsible of chemo- and radiotherapy refractoriness. According to the current carcinogenesis theory, CSCs represent the tumour-initiating cell (TIC) fraction, the only clonogenic subpopulation able to originate a tumour mass. Consequently, the recently described isolation of TICs from hMPM, the proposed main pharmacological target for novel antitumoural drugs, may contribute to better dissect the biology and multidrug resistance pathways controlling hMPM growth. © 2012 The Authors. British Journal of Pharmacology © 2012 The

Pain management of musculoskeletal injuries in children: current state and future directions.

PubMed

Ali, Samina; Drendel, Amy L; Kircher, Janeva; Beno, Suzanne

2010-07-01

Pain is the most common reason for seeking health care in the Western world and is a contributing factor in up to 80% of all emergency department (ED) visits. In the pediatric emergency setting, musculoskeletal injuries are one of the most common painful presentations. Inadequate pain management during medical care, especially among very young children, can have numerous detrimental effects. No standard of care exists for the management of acute musculoskeletal injury-related pain in children. Within the ED setting, pain from such injuries has been repeatedly shown to be undertreated. Upon completion of this CME article, the reader should be better able to (1) distinguish multiple nonpharmacological techniques for minimizing and treating pain and anxiety in children with musculoskeletal injuries, (2) apply recent medical literature in deciding pharmacological strategies for the treatment of children with musculoskeletal injuries, and (3) interpret the basic principles of pharmacogenomics and how they relate to analgesic efficacy. Pediatric musculoskeletal injuries are both common and painful. There is growing evidence that, in addition to pharmacological therapy, nonpharmacological methods can be introduced to improve analgesia in the ED and after discharge. Traditionally, acetaminophen with codeine has been used to treat moderate orthopedic injury-related pain in children. Other oral opioids (hydrocodone, oxycodone) are gaining popularity, as well. Current data suggest that ibuprofen is at least as effective as acetaminophen-codeine and codeine alone. Medication compliance might be improved if adverse effects were minimized, and ibuprofen has been shown to have a similar or better adverse effect profile than the oral opioids to which it has been compared. Pharmacogenomic data show that nearly 50% of individuals have at least 1 reduced functioning allele resulting in suboptimal conversion of codeine to active analgesic, so it is not surprising that codeine

Ultrasound and radiology surrogate endpoints in pharmacological studies.

PubMed

Agewall, S; DeGroot, E; Marcos-Alberca, P; Zamorano, J L; Barrero, A A; Badano, L P; Perrone-Filardi, P

2012-09-01

Cardiovascular studies investigating therapeutic intervention with clinical endpoints are costly due to the need for considerable duration and large number of patients, or both. Therefore, for evaluation of novel cardiovascular drug efficacy, surrogate endpoints are used. Cardiovascular imaging endpoints have proven their worth. Sometimes the relevance of imaging is questioned and other methods are suggested instead. There is also some confusion about the strengths of imaging endpoints. The aim of the present paper is to review ultrasound and radiology imaging techniques as surrogate endpoints in pharmacological trials. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A method of chemiluminescence coupled with ultrafiltration for investigating the interaction between ibuprofen and human serum albumin.

PubMed

Xiong, Xunyu; Zhang, Qunzheng; Nan, Yefei; Gu, Xuefan

2013-01-01

In acidic media, ibuprofen substantially enhanced the weak chemiluminescence (CL) produced by sodium sulfite and potassium permanganate. The increased signals were linearly correlated with ibuprofen concentrations ranging from 1.2 × 10(-3) to 4.8 μM, with a detection limit of 4.8 × 10(-4) μM. Two ultrafiltration (UF) membranes were used to construct a unit for trapping 0.15 and 0.75 μM human serum albumin (HSA) and coupled online with the CL system. At low HSA concentrations, the numbers of bound molecules per binding site were calculated to be 0.9 for Sudlow site I and 6.2 for Sudlow site II. The association constants on these binding sites were 5.9 × 10(5) and 3.4 × 10(4) M(-1), respectively. Our CL-UF protocol presents a rapid and sensitive method for studies on drug-protein interaction. Copyright © 2012 John Wiley & Sons, Ltd.

Electrochemical detection and degradation of ibuprofen from water on multi-walled carbon nanotubes-epoxy composite electrode.

PubMed

Motoc, Sorina; Remes, Adriana; Pop, Aniela; Manea, Florica; Schoonman, Joop

2013-04-01

This work describes the electrochemical behaviour of ibuprofen on two types of multi-walled carbon nanotubes based composite electrodes, i.e., multi-walled carbon nanotubes-epoxy (MWCNT) and silver-modified zeolite-multi-walled carbon nanotubes-epoxy (AgZMWCNT) composites electrodes. The composite electrodes were obtained using two-roll mill procedure. SEM images of surfaces of the composites revealed a homogeneous distribution of the composite components within the epoxy matrix. AgZMWCNT composite electrode exhibited the better electrical conductivity and larger electroactive surface area. The electrochemical determination of ibuprofen (IBP) was achieved using AgZMWCNT by cyclic voltammetry, differential-pulsed voltammetry, square-wave voltammetry and chronoamperometry. The IBP degradation occurred on both composite electrodes under controlled electrolysis at 1.2 and 1.75 V vs. Ag/AgCl, and IBP concentration was determined comparatively by differential-pulsed voltammetry, under optimized conditions using AgZMWCNT electrode and UV-Vis spectrophotometry methods to determine the IBP degradation performance for each electrode. AgZMWCNT electrode exhibited a dual character allowing a double application in IBP degradation process and its control.

Evaluation of analgesic and anti-inflammatory activity of a combination of tramadol-ibuprofen in experimental animals.

PubMed

Suthakaran, Chidambarann; Kayalvizhi, Muniyagounder K; Nithya, Karnam; Raja, Thozhudalangudy Ar

2017-01-01

Pain is the major concern of patients attending dental clinics, and satisfactory pain relief has always been difficult to achieve. Since the pathophysiology of pain is a complex, central and peripheral nervous system process, combined analgesic regimens with different mechanisms of action as a multimodal approach are becoming popular among the clinicians and dentists. The aim of the present study was to evaluate the analgesic and anti-inflammatory activity of ibuprofen and tramadol when used alone or in combination in animal models of pain and inflammation. The animals were divided into six groups with six animals in each group. Analgesic activity was assessed by hot plate method in rats and by acetic acid-induced writhing test in mice. Paw edema model in rats after induction with 0.1 mL of 1% carrageenan was used to assess the anti-inflammatory activity. Analysis of variance followed by Tukey's honestly significant difference post hoc test was used for statistical analysis. Combined use of tramadol and ibuprofen provided enhanced analgesic and anti-inflammatory effects in animal models of pain and inflammation.

Degradation of ibuprofen by hydrodynamic cavitation: Reaction pathways and effect of operational parameters.

PubMed

Musmarra, Dino; Prisciandaro, Marina; Capocelli, Mauro; Karatza, Despina; Iovino, Pasquale; Canzano, Silvana; Lancia, Amedeo

2016-03-01

Ibuprofen (IBP) is an anti-inflammatory drug whose residues can be found worldwide in natural water bodies resulting in harmful effects to aquatic species even at low concentrations. This paper deals with the degradation of IBP in water by hydrodynamic cavitation in a convergent-divergent nozzle. Over 60% of ibuprofen was degraded in 60 min with an electrical energy per order (EEO) of 10.77 kWh m(-3) at an initial concentration of 200 μg L(-1) and a relative inlet pressure pin=0.35 MPa. Five intermediates generated from different hydroxylation reactions were identified; the potential mechanisms of degradation were sketched and discussed. The reaction pathways recognized are in line with the relevant literature, both experimental and theoretical. By varying the pressure upstream the constriction, different degradation rates were observed. This effect was discussed according to a numerical simulation of the hydroxyl radical production identifying a clear correspondence between the maximum kinetic constant kOH and the maximum calculated OH production. Furthermore, in the investigated experimental conditions, the pH parameter was found not to affect the extent of degradation; this peculiar feature agrees with a recently published kinetic insight and has been explained in the light of the intermediates of the different reaction pathways. Copyright © 2015 Elsevier B.V. All rights reserved.

The Efficacy of Non-Pharmacological Interventions on Brain-Derived Neurotrophic Factor in Schizophrenia: A Systematic Review and Meta-Analysis.

PubMed

Sanada, Kenji; Zorrilla, Iñaki; Iwata, Yusuke; Bermúdez-Ampudia, Cristina; Graff-Guerrero, Ariel; Martínez-Cengotitabengoa, Mónica; González-Pinto, Ana

2016-10-24

Several studies have investigated the relationship between non-pharmacological interventions (NPIs) and peripheral brain-derived neurotrophic factor (BDNF) in schizophrenia patients. We conducted a systematic review and meta-analysis to review the efficacy of NPIs on peripheral serum and plasma BDNF in subjects with schizophrenia (including schizoaffective disorder). Meta-analyses were conducted to examine the effects of NPIs on blood BDNF levels by using the standardized mean differences (SMDs) between the intervention groups and controls. In total, six randomized controlled trials with 289 participants were included. Of them, five studies used exercise, physical training or diet products. One study used cognitive training. Overall, the BDNF levels in the NPI group increased significantly compared with the control groups (SMD = 0.95, 95% confidence interval (CI) = 0.07 to 1.83, p = 0.03). Subgroup analyses indicated beneficial effects of a non-exercise intervention on peripheral BDNF levels (SMD = 0.41, 95% CI = 0.08 to 0.74, p = 0.01). Meta-regression analyses showed that the completion rate influenced the variation in SMD ( p = 0.01). Despite insufficient evidence to draw a conclusion, our results suggest that use of NPIs as adjunctive treatments, specifically non-exercise interventions, may affect positively serum or plasma BDNF in patients with schizophrenia.

Molecular and clinical pharmacology of intranasal corticosteroids: clinical and therapeutic implications.

PubMed

Derendorf, H; Meltzer, E O

2008-10-01

Intranasal corticosteroids (INSs) are effective treatments for allergic rhinitis, rhinosinusitis, and nasal polyposis. In recent years, increased understanding of corticosteroid and glucocorticoid receptor pharmacology has enabled the development of molecules designed specifically to achieve potent, localized activity with minimal risk of systemic exposure. Pharmacologic potency studies using affinity and other assessments have produced similar rank orders of potency, with the most potent being mometasone furoate, fluticasone propionate, and its modification, fluticasone furoate. The furoate and propionate ester side chains render these agents highly lipophilic, which may facilitate their absorption through nasal mucosa and uptake across phospholipid cell membranes. These compounds demonstrate negligible systemic absorption. Systemic absorption rates are higher among the older corticosteroids (flunisolide, beclomethasone dipropionate, triamcinolone acetonide, and budesonide), which have bioavailabilities in the range of 34-49%. Studies, including 1-year studies with mometasone furoate, fluticasone propionate, and budesonide that evaluated potential systemic effects of INSs in children have generally found no adverse effects on hypothalamic-pituitary-adrenal axis function or growth. Clinical data suggest no significant differences in efficacy between the INSs. Theoretically, newer agents with lower systemic availability may be preferable, and may come closer to the pharmacokinetic/pharmacologic criteria for the ideal therapeutic choice.

Safety of oral ibuprofen--analysis of data from the spontaneous reporting system in Poland.

PubMed

Kuchari, Ernest; Han, Stanisław; Karłowicz-Bodalska, Katarzyna; Miśkiewicz, Katarzyna; Kutycka, Elzbieta

2014-01-01

Ibuprofen is a popular over-the-counter, non-steroidal anti-inflammatory medication, frequently used for the relief of fever, headaches, menstrual and other minor pains as well as a major active ingredient in numerous cold preparations. We analyzed sales volume and data obtained from the monitoring of spontaneous reports on the adverse effects of IBUM soft capsules, IBUM Forte soft capsules, and IBUM oral suspension 100 mg/5 mL collected by the manufacturer (PPF HASCO-LEK S.A. Wroclaw, Poland) and National Monitoring Center in Warszawa in the period between October 2002 and June 2012. A total of 19,644,797 units of IBUM soft capsules 200 mg, 5,678,164 units of IBUM Forte soft capsules 400 mg and 4,333,325 units of IBUM oral suspension 100 mg/5 mL (29,656,286 units altogether) produced by PPF HASCO-LEK S.A. Wrodcaw, P'oland were marketed during the period analyzed. There were 5 spontaneous reports regarding these medications registered in Poland in the period analyzed. Forms of oral ibuprofen are very safe medication rarely causing adverse effects; nevertheless, the existing spontaneous monitoring system of adverse effects in Poland is not sensitive enough to detect all adverse effects and needs improvement.

Contribution of microorganisms to non-extractable residue formation during biodegradation of ibuprofen in soil.

PubMed

Nowak, Karolina M; Girardi, Cristobal; Miltner, Anja; Gehre, Matthias; Schäffer, Andreas; Kästner, Matthias

2013-02-15

Non-extractable residues (NER) formed during biodegradation of organic contaminants in soil are considered to be mainly composed of parent compounds or their primary metabolites with hazardous potential. However, in the case of biodegradable organic compounds, the soil NER may also contain microbial biomass components, for example fatty acids (FA) and amino acids (AA). After cell death, these biomolecules are subsequently incorporated into non-living soil organic matter (SOM) and are stabilised ultimately forming hardly extractable residues of biogenic origin. We investigated biodegradation of (13)C(6)-ibuprofen, in particular the metabolic incorporation of the (13)C-label into FA and AA and their fate in soil over 90 days. (13)C-FA and (13)C-AA amounts in the living microbial biomass fraction initially increased, then decreased over time and were continuously incorporated into the non-living SOM pool. The (13)C-FA in the non-living SOM remained stable from day 59 whereas the contents of (13)C-AA slightly increased until the end. After 90 days, nearly all NER were biogenic as they were made up almost completely by natural biomass compounds. The presented data demonstrated that the potential environmental risks related to the ibuprofen-derived NER are overestimated. Copyright © 2012 Elsevier B.V. All rights reserved.

A controlled release of ibuprofen by systematically tailoring the morphology of mesoporous silica materials

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

Qu Fengyu; Chemistry and Pharmaceutical College, Jiamusi University, Jiamusi 154007; Zhu Guangshan

2006-07-15

A series of mesoporous silica materials with similar pore sizes, different morphologies and variable pore geometries were prepared systematically. In order to control drug release, ibuprofen was employed as a model drug and the influence of morphology and pore geometry of mesoporous silica on drug release profiles was extensively studied. The mesoporous silica and drug-loaded samples were characterized by X-ray diffraction, Fourier transform IR spectroscopy, N{sub 2} adsorption and desorption, scanning electron microscopy, and transmission electron microscopy. It was found that the drug-loading amount was directly correlated to the Brunauer-Emmett-Teller surface area, pore geometry, and pore volume; while the drugmore » release profiles could be controlled by tailoring the morphologies of mesoporous silica carriers. - Graphical abstract: The release of ibuprofen is controlled by tailoring the morphologies of mesoporous silica. The mesoporous silica and drug-loaded samples are characterized by powder X-ray diffraction, Fourier transform IR spectroscopy, N{sub 2} adsorption and desorption, scanning electron microscopy, and transmission electron microscopy. The drug-loading amount is directly correlated to the Brunauer-Emmett-Teller surface area, pore geometry, and pore volume; while the drug release profiles can be controlled by tailoring the morphologies of mesoporous silica carriers.« less

Short-term tests with a pilot sewage plant and biofilm reactors for the biological degradation of the pharmaceutical compounds clofibric acid, ibuprofen, and diclofenac.

PubMed

Zwiener, C; Frimmel, F H

2003-06-20

The biodegradation of three active compounds of pharmaceuticals clofibric acid, ibuprofen, and diclofenac was investigated in short-term tests with a pilot sewage plant (PSP) and biofilm reactors (BFR, oxic and anoxic) as model systems for municipal sewage treatment. The PSP was characterized with respect to mixing behavior, the BFR with respect to biofilm content and sorption of the pharmaceutical compounds. The short-term experiments were carried out for 55 h in the PSP and for 48 h in the BFR. The concentration of the pharmaceuticals was in the microgram per liter range in presence of readily biodegradable substances in the milligram per liter range. Therefore, a too short time period and too low concentration to promote adaption of the microorganisms were applied. Under the operating conditions applied the biodegradation of the lipid lowering agent clofibric acid and the analgesic agents ibuprofen and diclofenac in the oxic BFR resembled that in the PSP. Clofibric acid and diclofenac were not eliminated and reached a level of approximately 95% of their initial concentration, whereas the concentration of ibuprofen was decreased to approximately 40% in the PSP and to approximately 35% in the oxic BFR. Both systems showed, therefore, an inherent ability for ibuprofen biodegradation. Elimination in the anoxic BFR resulted in a decrease of the concentration of all three substances to values between 60 and 80% of their initial concentration. In contrast to the PSP acetone revealed as inhibitor in the BFR. In both systems acetone was not degraded in the short-term tests.

Ultrasound-assisted magnetic dispersive solid-phase microextraction: A novel approach for the rapid and efficient microextraction of naproxen and ibuprofen employing experimental design with high-performance liquid chromatography.

PubMed

Ghorbani, Mahdi; Chamsaz, Mahmoud; Rounaghi, Gholam Hossein

2016-03-01

A simple, rapid, and sensitive method for the determination of naproxen and ibuprofen in complex biological and water matrices (cow milk, human urine, river, and well water samples) has been developed using ultrasound-assisted magnetic dispersive solid-phase microextraction. Magnetic ethylendiamine-functionalized graphene oxide nanocomposite was synthesized and used as a novel adsorbent for the microextraction process and showed great adsorptive ability toward these analytes. Different parameters affecting the microextraction were optimized with the aid of the experimental design approach. A Plackett-Burman screening design was used to study the main variables affecting the microextraction process, and the Box-Behnken optimization design was used to optimize the previously selected variables for extraction of naproxen and ibuprofen. The optimized technique provides good repeatability (relative standard deviations of the intraday precision 3.1 and 3.3, interday precision of 5.6 and 6.1%), linearity (0.1-500 and 0.3-650 ng/mL), low limits of detection (0.03 and 0.1 ng/mL), and a high enrichment factor (168 and 146) for naproxen and ibuprofen, respectively. The proposed method can be successfully applied in routine analysis for determination of naproxen and ibuprofen in cow milk, human urine, and real water samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pharmacological therapy for amblyopia

PubMed Central

Singh, Anupam; Nagpal, Ritu; Mittal, Sanjeev Kumar; Bahuguna, Chirag; Kumar, Prashant

2017-01-01

Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time), penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents. PMID:29018759

2011 Annual Meeting of the Safety Pharmacology Society: an overview.

PubMed

Cavero, Icilio

2012-03-01

The keynote address of 2011 Annual Meeting of the Safety Pharmacology Society examined the known and the still to be known on drug-induced nephrotoxicity. The nominee of the Distinguished Service Award Lecture gave an account of his career achievements particularly on the domain of chronically instrumented animals for assessing cardiovascular safety. The value of Safety Pharmacology resides in the benefits delivered to Pharma organizations, regulators, payers and patients. Meticulous due diligence concerning compliance of Safety Pharmacology studies to best practices is an effective means to ensure that equally stringent safety criteria are applied to both in-licensed and in-house compounds. Innovative technologies of great potential for Safety Pharmacology presented at the meeting are organs on chips (lung, heart, intestine) displaying mechanical and biochemical features of native organs, electrical field potential (MEA) or impedance (xCELLigence Cardio) measurements in human induced pluripotent stem cell-derived cardiomyocytes for unveiling cardiac electrophysiological and mechanical liabilities, functional human airway epithelium (MucilAir™) preparations with unique 1-year shelf-life for acute and chronic in vitro evaluation of drug efficacy and toxicity. Custom-designed in silico and in vitro assay platforms defining the receptorome space occupied by chemical entities facilitate, throughout the drug discovery phase, the selection of candidates with optimized safety profile on organ function. These approaches can now be complemented by advanced computational analysis allowing the identification of compounds with receptorome, or clinically adverse effect profiles, similar to those of the drug candidate under scrutiny for extending the safety assessment to potential liability targets not captured by classical approaches. Nonclinical data supporting safety can be quite reassuring for drugs with a discovered signal of risk. However, for marketing authorization

Russian guidelines for the management of COPD: algorithm of pharmacologic treatment

PubMed Central

Aisanov, Zaurbek; Avdeev, Sergey; Arkhipov, Vladimir; Belevskiy, Andrey; Chuchalin, Alexander; Leshchenko, Igor; Ovcharenko, Svetlana; Shmelev, Evgeny; Miravitlles, Marc

2018-01-01

The high prevalence of COPD together with its high level of misdiagnosis and late diagnosis dictate the necessity for the development and implementation of clinical practice guidelines (CPGs) in order to improve the management of this disease. High-quality, evidence-based international CPGs need to be adapted to the particular situation of each country or region. A new version of the Russian Respiratory Society guidelines released at the end of 2016 was based on the proposal by Global Initiative for Obstructive Lung Disease but adapted to the characteristics of the Russian health system and included an algorithm of pharmacologic treatment of COPD. The proposed algorithm had to comply with the requirements of the Russian Ministry of Health to be included into the unified electronic rubricator, which required a balance between the level of information and the simplicity of the graphic design. This was achieved by: exclusion of the initial diagnostic process, grouping together the common pharmacologic and nonpharmacologic measures for all patients, and the decision not to use the letters A–D for simplicity and clarity. At all stages of the treatment algorithm, efficacy and safety have to be carefully assessed. Escalation and de-escalation is possible in the case of lack of or insufficient efficacy or safety issues. Bronchodilators should not be discontinued except in the case of significant side effects. At the same time, inhaled corticosteroid (ICS) withdrawal is not represented in the algorithm, because it was agreed that there is insufficient evidence to establish clear criteria for ICSs discontinuation. Finally, based on the Global Initiative for Obstructive Lung Disease statement, the proposed algorithm reflects and summarizes different approaches to the pharmacological treatment of COPD taking into account the reality of health care in the Russian Federation. PMID:29386887

Russian guidelines for the management of COPD: algorithm of pharmacologic treatment.

PubMed

Aisanov, Zaurbek; Avdeev, Sergey; Arkhipov, Vladimir; Belevskiy, Andrey; Chuchalin, Alexander; Leshchenko, Igor; Ovcharenko, Svetlana; Shmelev, Evgeny; Miravitlles, Marc

2018-01-01

The high prevalence of COPD together with its high level of misdiagnosis and late diagnosis dictate the necessity for the development and implementation of clinical practice guidelines (CPGs) in order to improve the management of this disease. High-quality, evidence-based international CPGs need to be adapted to the particular situation of each country or region. A new version of the Russian Respiratory Society guidelines released at the end of 2016 was based on the proposal by Global Initiative for Obstructive Lung Disease but adapted to the characteristics of the Russian health system and included an algorithm of pharmacologic treatment of COPD. The proposed algorithm had to comply with the requirements of the Russian Ministry of Health to be included into the unified electronic rubricator, which required a balance between the level of information and the simplicity of the graphic design. This was achieved by: exclusion of the initial diagnostic process, grouping together the common pharmacologic and nonpharmacologic measures for all patients, and the decision not to use the letters A-D for simplicity and clarity. At all stages of the treatment algorithm, efficacy and safety have to be carefully assessed. Escalation and de-escalation is possible in the case of lack of or insufficient efficacy or safety issues. Bronchodilators should not be discontinued except in the case of significant side effects. At the same time, inhaled corticosteroid (ICS) withdrawal is not represented in the algorithm, because it was agreed that there is insufficient evidence to establish clear criteria for ICSs discontinuation. Finally, based on the Global Initiative for Obstructive Lung Disease statement, the proposed algorithm reflects and summarizes different approaches to the pharmacological treatment of COPD taking into account the reality of health care in the Russian Federation.

Effect of Ibuprofen Dose on Platelet Aggregation and Coagulation in Blood Samples From Pigs

DTIC Science & Technology

2015-03-01

is not known and would be more of an issue with chronic misuse of the drug. Aspirin is another widely used NSAID. Despite similar anti-inflammatory...analgesic, and antipyretic effects, different profiles of actions have been observed in Aspirin and ibupro- fen. At equivalent effective doses of...ibuprofen (2,400 mg/day, equivalent to 3 + in this study) and aspirin (3,900 mg/day), liver function and platelet aggregation are more adversely affected by

Effect of ibuprofen vs acetaminophen on postpartum hypertension in preeclampsia with severe features: a double-masked, randomized controlled trial.

PubMed

Blue, Nathan R; Murray-Krezan, Cristina; Drake-Lavelle, Shana; Weinberg, Daniel; Holbrook, Bradley D; Katukuri, Vivek R; Leeman, Lawrence; Mozurkewich, Ellen L

2018-06-01

Nonsteroidal antiinflammatory drug use has been shown to increase blood pressure in nonpregnant adults. Because of this, the American College of Obstetricians and Gynecologists suggests avoiding their use in women with postpartum hypertension; however, evidence to support this recommendation is lacking. Our goal was to test the hypothesis that nonsteroidal antiinflammatory drugs, such as ibuprofen, adversely affect postpartum blood pressure control in women with preeclampsia with severe features. At delivery, we randomized women with preeclampsia with severe features to receive around-the-clock oral dosing with either 600 mg of ibuprofen or 650 mg of acetaminophen every 6 hours. Dosing began within 6 hours after delivery and continued until discharge, with opioid analgesics available as needed for breakthrough pain. Study drugs were encapsulated in identical capsules such that patients, nurses, and physicians were masked to study allocation. Exclusion criteria were serum aspartate aminotransferase or alanine aminotransferase >200 mg/dL, serum creatinine >1.0 mg/dL, infectious hepatitis, gastroesophageal reflux disease, age <18 years, or current incarceration. Our primary outcome was the duration of severe-range hypertension, defined as the time (in hours) from delivery to the last blood pressure ≥160/110 mm Hg. Secondary outcomes were time from delivery to last blood pressure ≥150/100 mm Hg, mean arterial pressure, need for antihypertensive medication at discharge, prolongation of hospital stay for blood pressure control, postpartum use of short-acting antihypertensives for acute blood pressure control, and opioid use for breakthrough pain. We analyzed all outcome data according to intention-to-treat principles. We assessed 154 women for eligibility, of whom 100 met entry criteria, agreed to participate, and were randomized to receive postpartum ibuprofen or acetaminophen for first-line pain control. Seven patients crossed over or did not receive their