Pharmacodynamic evaluation of intragastric pH and implications for famotidine dosing in the prophylaxis of non-steroidal anti-inflammatory drug induced gastropathy-a proof of concept analysis.

PubMed

Kent, Jeffery D; Holt, Robert J; Jung, Donald; Tidmarsh, George F; Grahn, Amy Y; Ball, Julie; Peura, David A

2014-01-01

Famotidine given at a dose of 80 mg/day is effective in preventing NSAID-induced gastropathy. The aim of this proof of concept study was to compare twice a day (BID) vs 3-times a day (TID) administration of this total dose of famotidine on intragastric pH in healthy volunteers. Two analyses were undertaken: (1) a 13 subject controlled cross-over 24-h intragastric pH evaluation of the BID and TID administration of 80 mg/day of famotidine, as well as measures for drug accumulation over 5 days (EudraCT, number 2006-002930-39); and (2) a pharmacokinetic (PK)/pharmacodynamic (PD) model which predicted steady-state famotidine plasma concentrations and pH of the two regimens. For the cross-over study, gastric pH was above 3.5 for a mean of 20 min longer for TID dosing compared to BID dosing on Day 1. On Day 5, the mean time above this threshold was higher with the BID regimen by ∼25 min. For pH 4, subjects' gastric pH was above this pH value for a mean of 25 min longer for TID dosing compared to BID dosing on Day 1. For Day 5, the pH was above 4 for ∼45 min longer with the TID regimen as compared with the BID regimen. The mean 24-h gastric pH values when taken in the upright position trended higher for the TID dosing period compared to the BID regimen on Day 1. The steady-state simulation model indicated that, following TID dosing, intragastric pH will be above 3 for 24 h vs 16 h for the BID regimen. There was no evidence for plasma accumulation of famotidine with TID dosing as compared to BID dosing from either analysis. The data indicate that overall more time is spent above the acidic threshold pH values when 80 mg/day of famotidine is administered TID vs BID. Key limitations included small study size with a short duration and lack of a baseline examination, but was compensated for by the cross-over and PK/PD modeling design. Although most of the comparisons in this proof of concept study were not statistically significant these results have

Comparison of the effect of the antacid Rennie versus low-dose H2-receptor antagonists (ranitidine, famotidine) on intragastric acidity.

PubMed

Netzer, P; Brabetz-Höfliger, A; Bründler, R; Flogerzi, B; Hüsler, J; Halter, F

1998-04-01

Symptoms of functional dyspepsia are common and patients often self-medicate with antacids, or with low-dose H2-antagonists which are available as over-the-counter medications. To date, there has been limited information available comparing the effects on intragastric acidity of these two types of over-the-counter medication. Therefore we studied the effect of the antacid Rennie and two H2-antagonists on the intragastric pH of fasting volunteers. Sixteen healthy, fasting volunteers were randomized into a double-blind, placebo-controlled, four-way crossover study comparing Rennie (calcium-magnesium carbonate) 1360 mg, ranitidine 75 mg, famotidine 10 mg and placebo. Their effect on gastric pH was monitored by a 4-h gastric pH-metry. The primary efficacy parameter was the time lag before an intragastric pH > 3.0 was reached after drug administration. The median time lag before pH > 3.0 was reached after drug administration was 5.8 min for Rennie, 64.9 min for ranitidine, 70.1 min for famotidine and 240.0 min for placebo. The percentage of time with values of pH > 3.0 was 10.4% for Rennie, 61.4% for ranitidine, 56.6% for famotidine and 1.4% for placebo. The onset of action in fasting volunteers was significantly faster with the antacid than with the two H2-antagonists. The duration of action was significantly longer with an H2-antagonist than with the antacid. This suggests that the two products should be used for different indications: antacids are superior for rapid pain relief, whereas H2-antagonists might be better for symptom prophylaxis--for example for nocturnal dyspepsia.

Spectrofluorimetric analysis of famotidine in pharmaceutical preparations and biological fluids by derivatization with benzoin

NASA Astrophysics Data System (ADS)

Alamgir, Malik; Khuhawar, Muhammad Yar; Memon, Saima Q.; Hayat, Amir; Zounr, Rizwan Ali

2015-01-01

A sensitive and simple spectrofluorimetric method has been developed for the analysis of famotidine, from pharmaceutical preparations and biological fluids after derivatization with benzoin. The reaction was carried out in alkaline medium with measurement of fluorescence intensity at 446 nm with excitation wavelength at 286 nm. Linear calibration was obtained with 0.5-15 μg/ml with coefficient of determination (r2) 0.997. The factors affecting the fluorescence intensity were optimized. The pharmaceutical additives and amino acid did not interfere in the determination. The mean percentage recovery (n = 4) calculated by standard addition from pharmaceutical preparation was 94.8-98.2% with relative standard deviation (RSD) 1.56-3.34% and recovery from deproteinized spiked serum and urine of healthy volunteers was 98.6-98.9% and 98.0-98.4% with RSD 0.34-0.84% and 0.29-0.87% respectively.

Spectrofluorimetric analysis of famotidine in pharmaceutical preparations and biological fluids by derivatization with benzoin.

PubMed

Alamgir, Malik; Khuhawar, Muhammad Yar; Memon, Saima Q; Hayat, Amir; Zounr, Rizwan Ali

2015-01-05

A sensitive and simple spectrofluorimetric method has been developed for the analysis of famotidine, from pharmaceutical preparations and biological fluids after derivatization with benzoin. The reaction was carried out in alkaline medium with measurement of fluorescence intensity at 446 nm with excitation wavelength at 286 nm. Linear calibration was obtained with 0.5-15 μg/ml with coefficient of determination (r(2)) 0.997. The factors affecting the fluorescence intensity were optimized. The pharmaceutical additives and amino acid did not interfere in the determination. The mean percentage recovery (n=4) calculated by standard addition from pharmaceutical preparation was 94.8-98.2% with relative standard deviation (RSD) 1.56-3.34% and recovery from deproteinized spiked serum and urine of healthy volunteers was 98.6-98.9% and 98.0-98.4% with RSD 0.34-0.84% and 0.29-0.87% respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

[Evaluation of Dissolution Profiles of Famotidine from Over-the-counter Drugs].

PubMed

Saito, Yuji; Adachi, Naoki; Kato, Miki; Nadai, Masayuki

2018-03-27

  In recent years, self-medication has started to receive more attention in Japan owing to increasing medical costs and health awareness among people. One of the main roles of pharmacists in self-medication is to provide appropriate information regarding over-the-counter (OTC) drugs. However, pharmacists promoting the proper use of OTC drugs have little information on their formulation properties. In this study, we performed dissolution tests on both OTC drugs and ethical drug (ED) containing famotidine, and evaluated the differences in their dissolution profiles. Marked differences in dissolution profiles of OTC drugs were observed in test solutions at pH 1.2, 4.0, and 6.8 and in water. To evaluate the differences quantitatively, we calculated the lag time and dissolution rate constant from the dissolution profiles. Significant differences in lag times and dissolution rate constants between some OTC drugs and ED were observed. We also used similarity factor (f2), to quantify the similarity between dissolution profiles of OTC drugs and ED. f2 values less than 42 were observed in some OTC drugs, suggesting that these differences might influence absorption in vivo resulting in differences in their onset time and efficacy. The findings of this study will provide useful information for the promotion of proper use of OTC drugs.

Formulation design of taste-masked particles, including famotidine, for an oral fast-disintegrating dosage form.

PubMed

Mizumoto, Takao; Tamura, Tetsuya; Kawai, Hitoshi; Kajiyama, Atsushi; Itai, Shigeru

2008-04-01

In this study, the taste-masking of famotidine, which could apply to any fast-disintegrating tablet, was investigated using the spray-dry method. The target characteristics of taste-masked particles were set as follows: the dissolution rate is not to be more than 30% at 1 min and not less than 85% at 15 min, and the particle size is not to be more than 150 microm in diameter to avoid a gritty feeling in the mouth. The target dissolution profiles of spray-dried particles consisting of Aquacoat ECD30 and Eudragit NE30D or triacetin was accomplished by the screening of formulas and the appropriate lab-scale manufacturing conditions. Lab-scale testing produced taste-masked particles that met the formulation targets. On the pilot scale, spray-dried particles with attributes, such as dissolution rate and particle size, of the same quality were produced, and reproducibility was also confirmed. This confirmed that the spray-dry method produced the most appropriate taste-masked particles for fast-disintegrating dosage forms.

Utility of N-Bromosuccinimide for the Titrimetric and Spectrophotometric Determination of Famotidine in Pharmaceutical Formulations

PubMed Central

Zenita, O.; Basavaiah, K.

2011-01-01

Two titrimetric and two spectrophotometric methods are described for the assay of famotidine (FMT) in tablets using N-bromosuccinimide (NBS). The first titrimetric method is direct in which FMT is titrated directly with NBS in HCl medium using methyl orange as indicator (method A). The remaining three methods are indirect in which the unreacted NBS is determined after the complete reaction between FMT and NBS by iodometric back titration (method B) or by reacting with a fixed amount of either indigo carmine (method C) or neutral red (method D). The method A and method B are applicable over the range of 2–9 mg and 1–7 mg, respectively. In spectrophotometric methods, Beer's law is obeyed over the concentration ranges of 0.75–6.0 μg mL−1 (method C) and 0.3–3.0 μg mL−1 (method D). The applicability of the developed methods was demonstrated by the determination of FMT in pure drug as well as in tablets. PMID:21760785

Evaluation of the palatabilities in 10 different famotidine orally disintegrating tablets by combination of disintegration device and taste sensor.

PubMed

Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Uchida, Takahiro

2015-01-01

The purpose of this study was to evaluate the palatabilities of the original and nine generic versions of famotidine orally disintegrating tablets (FODTs) by means of disintegration times and bitterness intensities determined using in combination disintegration device and taste sensor comparison of human gustatory sensation tests. The disintegration times were determined using a new disintegration testing equipment for ODTs, the OD-mate and bitterness intensities were determined using the SA501C taste-sensing system. The disintegration time and bitterness of each FODT was evaluated in gustatory sensation tests. There was a good correlation between the disintegration times of 10 FODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of FODTs at 10, 20 and 30 s after starting the disintegration using the OD-mate and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. A combination of the OD-mate and the SA501C was capable of predicting the palatabilities, disintegration properties and bitterness intensity of FODTs.

Application of vibrational spectroscopy, thermal analyses and X-ray diffraction in the rapid evaluation of the stability in solid-state of ranitidine, famotidine and cimetidine.

PubMed

Jamrógiewicz, Marzena; Ciesielski, Aleksander

2015-03-25

This paper reports the study on applicability of Fourier transform infrared (FTIR), near-infrared (NIR) and Raman spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) for the estimation of the chemical stability and photostability of histamine H2-receptor antagonist substances. Ranitidine hydrochloride (RAN), famotidine (FAM) and cimetidine (CIM) were tested and differences in sensitivity were measured via soft independence modeling of class analogies (Simca) model. The low values of variations for FAM and CIM and high variations obtained for RAN using FTIR and NIR techniques indicated that these methods were suitable and applicable to classify the degradation of RAN. Examined methods are recommendable in the first technological stage of drug production, and the preclinical and clinical development of pharmaceuticals or their quality control. Copyright © 2015 Elsevier B.V. All rights reserved.

Control-release microcapsule of famotidine loaded biomimetic synthesized mesoporous silica nanoparticles: Controlled release effect and enhanced stomach adhesion in vitro.

PubMed

Li, Jing; Wang, Hongyu; Yang, Baixue; Xu, Lu; Zheng, Nan; Chen, Hongtao; Li, Sanming

2016-01-01

In the present work, control-release microcapsule of famotidine (FMT) loaded biomimetic synthesized mesoporous silica nanoparticles (B-MSNs) was developed, and controlled release effect and stomach adhesion of this formulation in vitro were mainly investigated. B-MSN was previously synthesized and it was amorphous mesoporous nanoparticles with helical channels. Cytotoxicity of B-MSN was studied using human breast cancer cells (MCF-7) and the result indicated that cytotoxicity of B-MSN can be neglected. After loading FMT into B-MSN, specific surface area, pore volume and pore diameter of B-MSN were obviously reduced. In vitro dissolution test showed that B-MSN had the ability to slow down FMT release for 15 min. In order to prolong controlled release effect and remained the advantage of B-MSN (improve drug stability due to its rigid silica framework), the combined application of control-release microcapsule (using cellulose and hydroxypropyl methylcellulose K15M as excipients) with B-MSN was designed. It was obvious that newly designed formulation significantly controlled FMT release with Fickian diffusion mechanism and showed enhanced stomach adhesion in vitro, which has significant value in widening the application of B-MSN in formulation design. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of FRG-8813, a new-type histamine H(2)-receptor antagonist, on the recurrence of gastric ulcer after healing by drug treatment in rats.

PubMed

Ajioka, H; Miyake, H; Matsuura, N

2000-08-01

We investigated the recurrence of ulcers in rats after treatment with FRG-8813, (+/-)-2-(furfurylsulfinyl)-N-[4- [4-(piperidinomethyl)-2-pyridyl] oxy-(Z)-2-butenyl] acetamide, a novel histamine H(2)-receptor antagonist. Chronic gastric ulcers were induced by serosa-searing with a hot metal bar, and the ulcer healing and recurrence after treatment with FRG-8813 or famotidine were evaluated by endoscopy for 160 days. At the dose of 30 mg/kg p. o., once daily, the treatment with FRG-8813 or famotidine for 60 days, which was stopped earlier if the ulcer had healed, accelerated the ulcer healing significantly. A subsequent follow-up study on the healed rats showed that the cumulative recurrence rate of rats healed by FRG-8813 was lower than that of naturally healed rats or rats healed by famotidine. In many cases of rats healed by FRG-8813, the regenerated mucosa was normal in contrast with the control of famotidine-healed animals. The mucosal regeneration index of the gastric ulcer after 10 days' administration of FRG-8813 was significantly higher than that obtained with famotidine. After cessation of the treatment with famotidine for 7 days, rebound hyperacidity was induced; but such rebound did not occur with FRG-8813. Considering the low recurrence rate of ulcers after FRG-8813 treatment, we suggest that FRG-8813 treatment may provide additional benefits in peptic ulcer therapy. Copyright 2000 S. Karger AG, Basel

Pharmacokinetics and absorption of the anticancer agents dasatinib and GDC-0941 under various gastric conditions in dogs--reversing the effect of elevated gastric pH with betaine HCl.

PubMed

Pang, Jodie; Dalziel, Gena; Dean, Brian; Ware, Joseph A; Salphati, Laurent

2013-11-04

Changes in gastric pH can impact the dissolution and absorption of compounds presenting pH-dependent solubility. We assessed, in dogs, the effects of gastric pH-modifying agents on the oral absorption of two weakly basic anticancer drugs, dasatinib and GDC-0941. We also tested whether drug-induced hypochlorhydria could be temporarily mitigated using betaine HCl. Pretreatments with pentagastrin, famotidine, betaine HCl, or combinations of famotidine and betaine HCl were administered orally to dogs prior to drug dosing. The gastric pH was measured under each condition for up to 7 h, and the exposure of the compounds tested was calculated. The average gastric pH in fasted dogs ranged from 1.45 to 3.03. Pentagastrin or betaine HCl treatments lowered the pH and reduced its variability between dogs compared to control animals. In contrast, famotidine treatment maintained gastric pH at values close to 7 for up to 5 h, while betaine HCl transiently reduced the pH to approximately 2 in the famotidine-treated dogs. Famotidine pretreatment lowered GDC-0941 exposure by 5-fold, and decreased dasatinib measurable concentrations 30-fold, compared to the pentagastrin-treated dogs. Betaine HCl restored GDC-0941 AUC in famotidine-treated dogs to levels achieved in control animals, and increased dasatinib AUC to 1.5-fold that measured in control dogs. The results confirmed the negative impact of acid-reducing agents on the absorption of weakly basic drugs. They also suggested that betaine HCl coadministration may be a viable strategy in humans treated with acid-reducing agents in order to temporarily reduce gastric pH and restore drug exposure.

Mitigation of indomethacin-induced gastric mucosal lesions by a potent specific type V phosphodiesterase inhibitor

PubMed Central

Karakaya, Kemal; Hanci, Volkan; Bektas, Sibel; Can, Murat; Ucan, Hamdi B; Emre, Ali Ugur; Tascılar, Oge; Turan, Isıl Ozkocak; Comert, Mustafa; Irkorucu, Oktay; Cakmak, Guldeniz Karadeniz

2009-01-01

AIM: To investigate the gastroprotective effect of vardenafil against indomethacin-induced gastric damage. METHODS: Forty-eight female Wistar albino rats were randomly divided into 6 groups. Group 1 received saline only. Group 2 (indomethacin) received indomethacin. Rats in group 3 and 4 were pretreated with different doses of famotidine. Group 5 and 6 were pretreated with different doses of vardenafil. Rats in groups 3 to 6 received 25 mg/kg indomethacin 30 min after pretreatment. The animals were sacrificed 6 h later and their stomachs were opened. Gastric lesions were counted and measured. The stomach of each animal was divided in two parts for histopathological examinations and nitric oxide (NO) and malondialdehyde (MDA) assays, respectively. RESULTS: There were no gastric mucosal lesion in the saline group but all rats in the indomethacin group had gastric mucosal ulcerations (ulcer count; 6.25 ± 3.49, and mean ulcer area; 21.00 ± 12.35). Ulcer counts were diminished with famotidine 5 mg/kg (4.12 ± 2.47, P > 0.05), 20 mg/kg (2.37 ± 4.43, P < 0.05), vardenafil 2 mg/kg (4.37 ± 3.06), and vardenafil 10 mgkg (1.25 ± 1.38, P < 0.05) compared to the indomethacin group. Gastric mucosal lesion areas were diminished with famotidine 5 mg/kg (8.62 ± 2.97, P < 0.001) , famotidine 20 mg/kg (0.94 ± 2.06, P < 0.001), vardenafil 2 mg/kg (6.62 ± 5.87, P < 0.001), and vardenafil 10 mg/kg (0.75 ± 0.88, P < 0.001) compared to the indomethacin group. MDA levels were significantly higher in indomethacin group (28.48 ± 14.51), compared to the famotidine 5 mg/kg (6,21 ± 1.88, P < 0.05), famotidine 20 mg/kg (5.88 ± 1.60. P < 0.05), vardenafil 2 mg/kg (15.87 ± 3.93, P < 0.05), and vardenafil 10 mg/kg (10.97 ± 4.50, P < 0.05). NO concentration in gastric tissues of the famotidine groups were significantly increased (P < 0.05), but the NO increases in the vardenafil groups were not statistically significant. Histopathology revealed diminished gastric damage for

A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia.

PubMed

Meskanen, Katarina; Ekelund, Heidi; Laitinen, Jarmo; Neuvonen, Pertti J; Haukka, Jari; Panula, Pertti; Ekelund, Jesper

2013-08-01

Histamine has important functions as regulator of several other key neurotransmitters. Patients with schizophrenia have lower histamine H1 receptor levels. Since a case report in 1990 of an effect of the H2 antagonist famotidine on negative symptoms in schizophrenia, some open-label trials have been performed, but no randomized controlled trial. Recently, it was shown that clozapine is a full inverse agonist at the H2 receptor. We performed a researcher-initiated, academically financed, double-blind, placebo-controlled, parallel-group, randomized trial with the histamine H2 antagonist famotidine in treatment-resistant schizophrenia. Thirty subjects with schizophrenia were randomized to have either famotidine (100 mg twice daily, n = 16) or placebo (n = 14) orally, added to their normal treatment regimen for 4 weeks. They were followed up weekly with the Scale for the Assessment of Negative Symptoms (SANS), the PANSS (Positive and Negative Syndrome Scale), and Clinical Global Impression (CGI) Scale. In the famotidine group, the SANS score was reduced by 5.3 (SD, 13.1) points, whereas in the placebo group the SANS score was virtually unchanged (mean change, +0.2 [SD, 9.5]). The difference did not reach statistical significance (P = 0.134) in Mann-Whitney U analysis. However, the PANSS Total score and the General subscore as well as the CGI showed significantly (P < 0.05) greater change in the famotidine group than in the placebo group. No significant adverse effects were observed. This is the first placebo-controlled, randomized clinical trial showing a beneficial effect of histamine H2 antagonism in schizophrenia. H2 receptor antagonism may provide a new alternative for the treatment of schizophrenia.

Rebamipide May Be Comparable to H2 Receptor Antagonist in Healing Iatrogenic Gastric Ulcers Created by Endoscopic Mucosal Resection: A Prospective Randomized Pilot Study

PubMed Central

Kim, Yu Jin; Lee, Sang Kil; Kim, Jie Hyun; Lee, Yong Chan

2010-01-01

Endoscopic mucosal resection (EMR) results in the formation of iatrogenic gastric ulcers and the optimal treatments for such ulcers are still unclear. We aimed to evaluate the efficacy of rebamipide in the management of EMR-induced ulcers by comparing it with an H2 receptor antagonist. After EMR, patients were randomly assigned into either rebamipide or famotidine groups. All patients received a one-week lansoprazole 30 mg q.d. therapy followed by three-week famotidine (20 mg b.i.d.) or rebamipide (100 mg t.i.d.) therapy. Four weeks after the treatments, ulcer sizes, stages, bleeding rates, and ulcer-related symptoms were compared using endoscopy and a questionnaire. A total of 63 patients were enrolled in this study. Finally, 51 patients were analyzed, 26 in rebamipide and 25 in famotidine group. Baseline characteristics were not significantly different between the two groups. Four weeks after EMR, the two groups were comparable in terms of ulcer reduction ratio (P=0.297), and ulcer stage (P=1.000). Moreover, no difference was observed with regard to ulcer-related symptoms, drug compliance, adverse drug event rates, and bleeding rates. Our data suggest that rebamipide is not inferior to famotidine in healing iatrogenic gastric ulcers, and could be a therapeutic option in the treatment of such ulcers. PMID:20358002

Using multiple pharmacoeconomic methods to conduct a cost-effectiveness analysis of histamine H2-receptor antagonists.

PubMed

McCoy, S; Blayney-Chandramouli, J; Mutnick, A

1998-12-15

A formulary decision at a health care institution was studied by using two pharmacoeconomic methods. A pharmacoeconomic study was undertaken to assess the impact of a 1995 formulary decision to designate cimetidine as the primary histamine H2-receptor antagonist (H2RA) and to restrict the use of famotidine. Consecutive patients receiving either i.v. cimetidine or famotidine for stress ulcer prophylaxis were reviewed during a two-month period in 1997, and information on demographics, dosage and duration of H2RA therapy, admission date, laboratory test values, and adverse drug reactions was collected. Data for 62 patients (43 cimetidine recipients and 19 famotidine recipients) were evaluated. Therapy was categorized as successful or failed, and the data were then evaluated by decision analysis to evaluate the cost-effectiveness of the agents and by multiattribute utility theory (MAUT) to incorporate a humanistic evaluation of the treatments, namely, the number of doses administered and the number of times dosages were changed. The decision tree revealed that the average cost of receiving cimetidine was $82.01 and the average cost of famotidine therapy was $92.45. The MAUT analysis showed that cimetidine was the preferred agent as long as cost was valued at greater than 60% of the decision-making process and efficacy remained equal between the two agents. Two pharmacoeconomic methods lent support to a formulary decision at a health care institution.

[Modern approach to the prevention and treatment of NSAID-gastropathy].

PubMed

Drozdov, V N; Kim, V A; Lazebnik, L B

2011-01-01

The article presents the results of the first Russian open randomized comparative multicenter study on the effectiveness of Famotidine in the prevention of NSAID-gastropathy--Barrier. In addition, were showen the results of studies of the drugs effect used for prevention of NSAID gastropathy (Famotidine, Lansoprazole, Misoprostol) for the synthesis of prostaglandins in the gastric mucosa in patients with osteoarthritis. Was shown the impact of alternative anti-inflammatory drug on the basis of an extract of ginger as joint pain, and the mucous upper gastrointestinal tract in patients with osteoarthritis.

Behavior of pharmaceuticals in waste water treatment plant in Japan.

PubMed

Matsuo, H; Sakamoto, H; Arizono, K; Shinohara, R

2011-07-01

The fate of pharmaceuticals in a wastewater treatment plant (WWTP) in Kumamoto, Japan with activated sludge treatment is reported. Selected pharmaceuticals were detected in influent. Results from the present study confirmed that Acetaminophen, Amoxicillin, Ampicillin and Famotidine were removed at a high rate (>90% efficiency). In contrast, removal efficiency of Ketoprofen, Losartan, Oseltamivir, Carbamazepine, and Diclofenac was relatively low (<50%). The selected pharmaceuticals were also detected in raw sludge. In digestive process, Indomethacin, Atenolol, Famotidine, Trimethoprim and Cyclofosamide were removed at a high (>70% efficiency). On the other hand, removal of Carbamazepine, Ketoprofen and Diclofenac was not efficient (<50%).

Physical and chemical stability of palonosetron hydrochloride with five common parenteral drugs during simulated Y-site administration.

PubMed

Kupie, Thomas C; Trusley, Craig; Ben, Michel; Trissel, Lawrence A

2008-09-15

The physical and chemical compatibility of palonosetron hydrochloride with atropine sulfate, famotidine, heparin sodium, lidocaine hydrochloride, and potassium chloride during simulated Y-site administration were studied. Test samples were prepared in duplicate by separately mixing 7.5-mL samples of undiluted palonosetron hydrochloride 50 microg/mL with 7.5-mL samples of atropine sulfate 0.4 mg/mL, famotidine 2 mg/mL, undiluted heparin sodium 100 units/mL, lidocaine hydrochloride 10 mg/mL, and potassium chloride 0.1 meq/mL diluted in 5% dextrose in colorless 15-mL borosilicate glass screw-cap culture tubes with polypropylene caps. Physical stability of the admixtures was assessed by visual examination and by measuring turbidity and particle size and content. Chemical stability of atropine sulfate, famotidine, heparin sodium, and lidocaine hydrochloride was assessed by stability-indicating high-performance liquid chromatography. Potassium chloride concentration was determined by indirect potentiometry using a potassiumion selective electrode. All of the samples of palonosetron hydrochloride with the test drugs were initially clear and colorless in normal fluorescent room light and when viewed with a Tyndall beam. Changes in turbidity for the samples were minor throughout the study. Measured particulates of 10 mum or larger were found to be few in number in all samples and remained so throughout the observation period. The admixtures remained colorless throughout the study. No loss of palonosetron hydrochloride occurred with any of the drugs over four hours. Similarly, little or no loss of the other drugs occurred in four hours. Palonosetron hydrochloride is physically and chemically stable with atropine sulfate, famotidine, heparin sodium, lidocaine hydrochloride, and potassium chloride during simulated Y-site administration.

Application of the BCS biowaiver approach to assessing bioequivalence of orally disintegrating tablets with immediate release formulations.

PubMed

Ono, Asami; Sugano, Kiyohiko

2014-11-20

The aim of this study was to compare the dissolution profiles of oral disintegrating tablets (ODTs) and immediate release (IR) formulations in order to experimentally validate the regulatory biowaiver scheme (BWS) for biopharmaceutical classification system (BCS) class III drugs. We examined six drugs that show clinical bioequivalence between the ODTs and IR formulations: taltirelin, olopatadine, droxidopa, famotidine, fexofenadine, and hydrochlorothiazide. The dissolution profiles of these drugs were evaluated using the compendium paddle apparatus at pH 1.2 and 6.8. Taltirelin and olopatadine showed very rapid dissolution and met the dissolution criteria in the BWS, whereas droxidopa, famotidine, fexofenadine, and hydrochlorothiazide did not. Furthermore, in the case of famotidine, fexofenadine, and hydrochlorothiazide, the ODTs and IR formulations showed dissimilar dissolution profiles. The dose-to-solubility ratio (D:S) of these drugs was larger than that of the other drugs. The results of this study suggest that extension of the BCS-BWS to ODTs and IR formulations of BCS class III drugs is appropriate. Furthermore, for BCS class III drugs with relatively high D:S, clinical bioequivalence would be achievable even when two formulations showed different dissolution profiles in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of esomeprazole on healing of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric ulcers in the presence of a continued NSAID treatment: Characterization of molecular mechanisms.

PubMed

Fornai, Matteo; Colucci, Rocchina; Antonioli, Luca; Awwad, Oriana; Ugolini, Clara; Tuccori, Marco; Fulceri, Federica; Natale, Gianfranco; Basolo, Fulvio; Blandizzi, Corrado

2011-01-01

Proton pump inhibitors promote ulcer repair in nonsteroidal anti-inflammatory drug (NSAID)-treated patients with ongoing NSAID-induced gastric toxicity, although the underlying mechanisms remain unclear. We examined the healing mechanisms of esomeprazole on NSAID-induced gastric ulcerations in the presence of a continued NSAID treatment. Ulcerations were induced in rats by oral indomethacin (6μmol/kg/day) for 14 days. Indomethacin administration was continued, alone or combined with equivalent acid inhibitory doses of esomeprazole (5μmol/kg/day), lansoprazole (15μmol/kg/day) or famotidine (20μmol/kg/day), for additional 7 days. Stomachs were then processed for: histomorphometric analysis of mucosal injury; mucosal levels of prostaglandin E(2) (PGE(2)) and malondialdehyde (MDA); expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), caspase-3, and cyclooxygenase-2 (COX-2) (Western blot); expression of Ki-67 (immunohistochemistry). Indomethacin for 14 days elicited mucosal damage, reduced PGE(2) levels and increased MDA. After additional 7 days, indomethacin induced the following effects: further enhancement of mucosal damage and MDA content; decrease in PGE(2) levels; increase in COX-2 and activated caspase-3 expression; decrease in VEGF, PCNA and Ki-67 expression. In the presence of indomethacin, esomeprazole and lansoprazole were more effective than famotidine in promoting resolution of mucosal damage. Concomitantly, esomeprazole and lansoprazole, but not famotidine, restored PCNA and Ki-67 expression, and normalized MDA levels. Moreover, esomeprazole, lansoprazole and famotidine partly counteracted caspase-3 activation, without affecting VEGF expression. The healing activity of esomeprazole on indomethacin-induced gastric ulcerations can be ascribed to two mechanisms: (1) acid-dependent reduction of pro-apoptotic signalling; (2) acid-independent restoration of proliferating/repairing pathways. Copyright © 2010

Effect of the novel histamine H2-antagonist 5,6-dimethyl-2-[4-[3-(1- piperidinomethyl)phenoxy]-(z)-2-butenylamino]-4(1H)-pyrimidine dihydrochloride on histamine-induced gastric acid secretion in Heidenhain pouch dogs.

PubMed

Uchida, M; Ohba, S; Ikarashi, Y; Misaki, N; Kawano, O

1993-08-01

Effects of IGN-2098 (5,6-dimethyl-2-[4-[3-(1-piperidinomethyl)phenoxy]- (z)-2-butenylamino]-4(1H)-pyrimidone dihydrochloride, CAS 126869-04-3) a novel histamine H2-antagonist, on histamine-induced gastric acid secretion were investigated in Heidenhain pouch dogs in comparison with those of famotidine, roxatidine acetate HCl and cimetidine. Orally administered IGN-2098 (0.03-1.0 mg/kg), famotidine (0.01-0.3 mg/kg), roxatidine acetate HCl (0.1-1.0 mg/kg) and cimetidine (0.3-3.0 mg/kg) showed dose-dependent inhibition on histamine-induced gastric acid secretion, and ED50 values of IGN-2098, famotidine, roxatidine acetate HCl and cimetidine were 0.077, 0.024, 0.200 and 0.585 mg/kg, respectively. IGN-2098 was effective even at 6 h after administration and ED50 value was 0.315 mg/kg. IGN-2098 was effective also by intravenous route. The inhibitory effect of IGN-2098 on histamine-induced gastric secretion was not affected by the repeated administration of IGN-2098 (1 mg/kg b.i.d. for 14 days). These results show that IGN-2098 is a potent and long acting antisecretory agent and is a useful antisecretory drug for the treatment of peptic ulcer disease.

Vismodegib

MedlinePlus

... cimetidine (Tagamet), famotidine (Pepcid), and ranitidine (Zantac); and proton-pump inhibitors such as dexlansoprazole (Dexilant), lansoprazole (Prevacid, in Prevpac), omeprazole (Prilosec, Zegerid), pantoprazole (Protonix), and rabeprazole (AcipHex). Your doctor may need to change the ...

[Efficacy evaluation of lafutidine for mild reflux esophagitis in Japanese patients].

PubMed

Ohara, Shuichi; Haruma, Ken; Kinoshita, Yoshikazu; Kusano, Motoyasu

2010-04-01

To evaluate the efficacy of lafutidine (20mg) , famotidine (40mg) and placebo in patients with mild reflux esophagitis (Grades A and B according to the Los Angeles classification) , a double-blind, multicenter, randomized clinical trial was performed for the first time in Japanese patients. In addition to each physician's evaluation, efficacy was evaluated by judging panels using images submitted by each physician. The healing rate after 8 weeks for lafutidine, famotidine and placebo were 67.7%, 56.6% and 41.2%, respectively. Lafutidine was significantly more effective than placebo (p=0.002, according to the judging panels) . Based on the evaluation of endoscopic images by the judging panels, 91 (27.1%) of 336 images submitted by each physician were judged to not be mucosal breaks. Judging panels are considered one of the ways to resolve the problem of the need to unify the criteria.

Effects of central histamine receptors blockade on GABA(A) agonist-induced food intake in broiler cockerels.

PubMed

Morteza, Zendehdel; Vahhab, Babapour; Hossein, Jonaidi

2008-02-01

In this study, the effect of intracerebroventricular (i.c.v) injection of H1, H2 and H3 antagonists on feed intake induced by GABA(A) agonist was evaluated. In Experiment 1, the animals received chloropheniramine, a H1 antagonist and then muscimol, a GABA(A) agonist. In Experiment 2, chickens received famotidine, a H2 receptor antagonist, prior to injection of muscimol. Finally in Experiment 3, the birds were injected with thioperamide, a H3 receptor antagonist and muscimol. Cumulative food intake was measured 15, 30, 45, 60, 90, 120, 150 and 180 min after injections. The results of this study indicated that effects of muscimol on food intake inhibited by pretreatment with chloropheneramine maleate (p < or = 0.05), significantly, while the famotidine and thioperamide were ineffective. These results suggest the existence of H1-receptor mediated histamine-GABA(A) receptor interaction on food intake in broiler cockerels.

Inhibitors of acid secretion can benefit gastric wound repair independent of luminal pH effects on the site of damage

PubMed Central

Demitrack, Elise S; Aihara, Eitaro; Kenny, Susan; Varro, Andrea; Montrose, Marshall H

2012-01-01

Background and aims The authors’ goal was to measure pH at the gastric surface (pHo) to understand how acid secretion affects the repair of microscopic injury to the gastric epithelium. Methods Microscopic gastric damage was induced by laser light, during confocal/two-photon imaging of pH-sensitive dyes (Cl-NERF, BCECF) that were superfused over the mucosal surface of the exposed gastric corpus of anaesthetised mice. The progression of repair was measured in parallel with pHo. Experimental conditions included varying pH of luminal superfusates, and using omeprazole (60 mg/kg ip) or famotidine (30 mg/kg ip) to inhibit acid secretion. Results Similar rates of epithelial repair and resting pHo values (~pH 4) were reported in the presence of luminal pH 3 or pH 5. Epithelial repair was unreliable at luminal pH 2 and pHo was lower (2.5±0.2, P <0.05 vs pH 3). Epithelial repair was slower at luminal pH 7 and pHo was higher (6.4±0.1, P<0.001). In all conditions, pHo increased adjacent to damage. At luminal pH 3 or pH 7, omeprazole reduced maximal damage size and accelerated epithelial repair, although only at pH 3 did omeprazole further increase surface pH above the level caused by imposed damage. At luminal pH 7, famotidine also reduced maximal damage size and accelerated epithelial repair. Neither famotidine nor omeprazole raised plasma gastrin levels during the time course of the experiments. Conclusions Epithelial repair in vivo is affected by luminal pH variation, but the beneficial effects of acutely blocking acid secretion extend beyond simply raising luminal and/or surface pH. PMID:21997560

Expression of HSP72 in the gastric mucosa is regulated by gastric acid in rats-Correlation of HSP72 expression with mucosal protection

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

Wada, Isao; Otaka, Michiro; Jin, Mario

2006-10-20

Background and aim: The real mechanism of adaptive cytoprotection in the gastric mucosa is not well established. In the present study, we investigated the effect of acid suppressing agents on a 72-kDa heat shock protein (HSP72) expression, which is known as endogenous cytoprotective factor, in the gastric mucosa. Also, the association of gastric mucosal protective function against HCl-challenge was compared between HSP72-induced and -reduced group. Materials and methods: Expression of HSP72 was measured by Western blotting in the gastric mucosa before and after administration of famotidine or omeprazole. The gastric mucosal protective function against 0.6 N HCl was compared betweenmore » control group and HSP72-reduced group. Also, the effect of increased expression of gastric HSP72 by additional administration of zinc sulfate or zinc L-carnosine, which is known as HSP72-inducer, on mucosal protective function was studied. Results: HSP72 expression in the gastric mucosa was reduced by acid suppressing agents. The lowest expression level of HSP72 was observed 12 h (famotidine, H2-receptor antagonist) or 48 h (omeprazole, proton pump inhibitor) after administration. The gastric mucosal protective ability against 0.6 N HCl was also reduced when HSP72 expression was decreased by famotidine or omeprazole. This phenomenon was reversed by HSP72 induction by additional administration of zinc derivatives. Conclusion: Our results might indicate that the expression of HSP72 in the gastric mucosa is physiologically regulated by gastric acid, and that HSP72 induction could be important in view of mucosal protection especially when HSP72 expression is reduced by administration of acid suppressing agents such as proton pump inhibitor or H2 receptor antagonist.« less

Near-Fatal Gastrointestinal Hemorrhage in a Child with Medulloblastoma on High Dose Dexamethasone.

PubMed

Yecies, Derek; Tawfik, Daniel; Damman, Jennifer; Thorson, Chad; Hong, David S; Grant, Gerald A; Bensen, Rachel; Damian, Mihaela

2017-07-07

A four-year-old female was admitted to a university-based children's hospital with a newly-diagnosed posterior fossa tumor. She was started on famotidine and high-dose dexamethasone and underwent gross total resection of a medulloblastoma. She was continued on dexamethasone and famotidine. She exhibited postoperative posterior fossa syndrome and was started on enteral feeds via the nasoduodenal tube. She had small gastrointestinal bleeds on postoperative days eight, 11, and 18, and was found to have a well-circumscribed posterior duodenal ulcer. On postoperative day 19, she suffered a massive life-threatening gastrointestinal bleed requiring aggressive resuscitation with blood products. She required an emergent laparotomy due to ongoing blood loss and she was found to have posterior duodenal wall erosion into her gastroduodenal artery. She recovered and subsequently began delayed chemotherapy. This case demonstrates a rare and life-threatening complication of high-dose dexamethasone therapy in the setting of posterior fossa pathology despite stress ulcer prophylaxis. We present a historical perspective with the review of the association between duodenal and intracranial pathology and the usage of high-dose dexamethasone in such cases.

Protective effects of ginger and marshmallow extracts on indomethacin-induced peptic ulcer in rats.

PubMed

Zaghlool, Sameh S; Shehata, Basim A; Abo-Seif, Ali A; Abd El-Latif, Hekma A

2015-01-01

Gastric ulcer is one of the most serious diseases. Most classic treatment lines produce adverse drug reactions. Therefore, this study aimed to investigate the protective effects of two natural extracts, namely ginger and marshmallow extracts, on indomethacin-induced gastric ulcer in rats. Animals were divided into five groups; a normal control group, an ulcer control group, and three treatment groups receiving famotidine (20 mg/kg), ginger (100 mg/kg), and marshmallow (100 mg/kg). Treatments were given orally on a daily basis for 14 days prior to a single intra-peritoneal administration of indomethacin (20 mg/kg). Indomethacin administration resulted in significant ulcerogenic effect evidenced by significant elevations in ulcer number, ulcer index, and blood superoxide dismutase activity accompanied by significant decreases in gastric mucosal nitric oxide and glutathione levels. In addition, elevations in gastric mucosal lipid peroxides and histamine content were observed. Alternatively, pretreatment with famotidine, ginger or marshmallow significantly corrected macroscopic and biochemical findings, supported microscopically by results of histopathological study. These results demonstrate that administration of either ginger or marshmallow extract could protect against indomethacin-induced peptic ulcer in rats presumably via their antioxidant properties and inhibition of histamine release.

Segmental dependent transport of low permeability compounds along the small intestine due to P-glycoprotein: the role of efflux transport in the oral absorption of BCS class III drugs.

PubMed

Dahan, Arik; Amidon, Gordon L

2009-01-01

The purpose of this study was to investigate the role of P-gp efflux in the in vivo intestinal absorption process of BCS class III P-gp substrates, i.e. high-solubility low-permeability drugs. The in vivo permeability of two H (2)-antagonists, cimetidine and famotidine, was determined by the single-pass intestinal perfusion model in different regions of the rat small intestine, in the presence or absence of the P-gp inhibitor verapamil. The apical to basolateral (AP-BL) and the BL-AP transport of the compounds in the presence or absence of various efflux transporters inhibitors (verapamil, erythromycin, quinidine, MK-571 and fumitremorgin C) was investigated across Caco-2 cell monolayers. P-gp expression levels in the different intestinal segments were confirmed by immunoblotting. Cimetidine and famotidine exhibited segmental dependent permeability through the gut wall, with decreased P(eff) in the distal ileum in comparison to the proximal regions of the intestine. Coperfusion of verapamil with the drugs significantly increased the permeability in the ileum, while no significant change in the jejunal permeability was observed. Both drugs exhibited significantly greater BL-AP than AP-BL Caco-2 permeability, indicative of net mucosal secretion. Concentration dependent decrease of this secretion was obtained by the P-gp inhibitors verapamil, erythromycin and quinidine, while no effect was evident by the MRP2 inhibitor MK-571 and the BCRP inhibitor FTC, indicating that P-gp is the transporter mediates the intestinal efflux of cimetidine and famotidine. P-gp levels throughout the intestine were inversely related to the in vivo permeability of the drugs from the different segments. The data demonstrate that for these high-solubility low-permeability P-gp substrates, P-gp limits in vivo intestinal absorption in the distal segments of the small intestine; however P-gp plays a minimal role in the proximal intestinal segments due to significant lower P-gp expression levels

The effect of pentadecapeptide BPC 157, H2-blockers, omeprazole and sucralfate on new vessels and new granulation tissue formation.

PubMed

Sikiric, P; Separovic, J; Anic, T; Buljat, G; Mikus, D; Seiwerth, S; Grabarevic, Z; Stancic-Rokotov, D; Pigac, B; Hanzevacki, M; Marovic, A; Rucman, R; Petek, M; Zoricic, I; Ziger, T; Aralica, G; Konjevoda, P; Prkacin, I; Gjurasin, M; Miklic, P; Artukovic, B; Tisljar, M; Bratulic, M; Mise, S; Rotkvic, I

1999-12-01

A clear protection of the gastrointestinal tract and an evident anti-inflammatory effect were shown for a novel stomach pentadecapeptide BPC 157 (i.p./i.g.) in comparison with several reference standards in various ulcer models along with a protection of endothelium and particular interaction with the NO-system. Thus, we evaluated whether this pentadecapeptide along with other gastroprotective agents could affect angiogenesis and the healing process in vivo using a procedure initially described by Szabo and co-workers. In each rat, two sterile sponges (1 x 1 x 0.25 cm; V = 0.25 mL) with the same quantities of BPC 157 (10 ng x mL(-1), 10 microg x mL(-1), 50 microg x kg(-1)) or reference agents (cimetidine: 10, 100, 500 mg x mL(-1); ranitidine: 2.5, 25, 250 mg x mL(-1); famotidine: 10, 50, 100 mg x mL(-1); omeprazole: 10, 50, 100 mg x mL(-1); sucralfate: 1, 5, 10 mg x mL(-1) were implanted subcutaneously in the lumbar region. The sponges were removed after 3 or 7 d, fixed in formalin, and processed for histologic and histochemical evaluation and morphometry assessment. Compared with the control values, the number of newly formed endothelial spaces inside newly formed granulation tissue was markedly increased in all animals treated with BPC 157, cimetidine, ranitidine, famotidine, sucralfate and omeprazole, a consistent finding noted after either 3 or 7 d. Compared with control values, markedly more granulation tissue was noted in the rats in the groups of animals treated with BPC 157 (50 microg) and in the rats treated with sucralfate in all dosages used, euthanized after 3 d. In all groups treated with H2-blockers however, similar values to those of controls were noted. Thus, it could be concluded that an evident angiogenic property was consistently noted for the novel pentadecapeptide BPC 157, H2-blockers (cimetidine, famotidine and ranitidine) and omeprazole, besides the well known angiogenic effect of sucralfate. Furthermore, unlike H2-blockers and omeprazole

Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin.

PubMed

Chan, Francis K L; Kyaw, Moe; Tanigawa, Tetsuya; Higuchi, Kazuhide; Fujimoto, Kazuma; Cheong, Pui Kuan; Lee, Vivian; Kinoshita, Yoshikazu; Naito, Yuji; Watanabe, Toshio; Ching, Jessica Y L; Lam, Kelvin; Lo, Angeline; Chan, Heyson; Lui, Rashid; Tang, Raymond S Y; Sakata, Yasuhisa; Tse, Yee Kit; Takeuchi, Toshihisa; Handa, Osamu; Nebiki, Hiroko; Wu, Justin C Y; Abe, Takashi; Mishiro, Tsuyoshi; Ng, Siew C; Arakawa, Tetsuo

2017-01-01

It is not clear whether H 2 -receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186. Copyright © 2017 AGA

Involvement of histaminergic and noradrenergic receptors in the oxytocin-induced food intake in neonatal meat-type chicks.

PubMed

Mirnaghizadeh, Seyed Vahid; Zendehdel, Morteza; Babapour, Vahab

2017-03-01

Oxytocin neurons have a physiological role in food intake and energy balance. Several studies have shown that central histaminergic and adrenergic systems synapse on oxytocin neurons but there is no information for their interaction on food intake regulation in birds. The purpose of this study was to examine the effects of intracerebroventricular (ICV) injection of α-fluoromethylhistidine (α-FMH, histidine decarboxylase inhibitor), chlorpheniramine (histamine H1 receptors antagonist), famotidine (histamine H2 receptors antagonist), thioperamide (histamine H3 receptors antagonist), prazosin (α1 receptor antagonist), yohimbine (α2 receptor antagonist), metoprolol (β1 adrenergic receptor antagonist), ICI 118,551 (β2 adrenergic receptor antagonist) and SR59230R (β3 adrenergic receptor antagonist) on oxytocin-induced hypophagia in 3-h food-deprived (FD 3 ) neonatal broiler chicken. In Experiment 1, 3 h-fasted chicks were given an ICV injection of saline, α-FMH (250 nmol), oxytocin (10 μg) and co-injection of α-FMH + oxytocin. Experiments 2-9 were similar to experiment 1 except birds were injected with chlorpheniramine (300 nmol), famotidine (82 nmol), thioperamide (300 nmol), prazosin (10 nmol), yohimbine (13 nmol), metoprolol (24 nmol), ICI 118,551(5 nmol) and SR59230R (20 nmol) instead of α-FMH, respectively. After injection cumulative food intake was measured until 120 min post injection. According to the results, ICV injection of oxytocin significantly decreased food intake in broiler chickens (P < 0.001). ICV injection of α-FMH significantly attenuated hypophagic effect of oxytocin (P < 0.001). Also, co-injection of chlorpheniramine plus oxytocin significantly decreased the effect of oxytocin on food intake (P < 0.001). Co-administration of thioperamide and oxytocin significantly amplified hypophagic effect of oxytocin in chickens (P < 0.001). In addition, ICI 118,551 attenuated hypophagic effect of oxytocin (P < 0.001); while

Quantum mechanical, spectroscopic studies (FT-IR, FT-Raman, NMR, UV) and normal coordinates analysis on 3-([2-(diaminomethyleneamino) thiazol-4-yl] methylthio)-N'-sulfamoylpropanimidamide

NASA Astrophysics Data System (ADS)

Muthu, S.; Uma Maheswari, J.; Sundius, Tom

2013-05-01

Famotidine (3-([2-(diaminomethyleneamino) thiazol-4-yl] methylthio)-N'-sulfamoylpropanimidamide) is a histamine H2-receptor antagonist that inhibits stomach acid production, and it is commonly used in the treatment of peptic ulcer disease (PUD) and gastroesophageal reflux disease (GERD/GORD). Quantum chemical calculations of the equilibrium geometry of famotidine in the ground state were carried out using density functional theory (DFT/B3LYP) with the 6-311G(d,p) basis set. In addition, harmonic vibrational frequencies, infrared intensities and Raman activities were calculated at the same level of theory. A detailed interpretation of the infrared and Raman spectrum of the drug is also reported. Theoretical simulations of the FT-IR, and FT-Raman spectra of the title compound have been calculated. Good correlations between the experimental 1H and 13C NMR chemical shifts and calculated GIAO shielding tensors were found. The results of the energy and oscillator strength calculations by time-dependent density functional theory (TD-DFT) supplement the experimental findings. Total and partial density of state (TDOS and PDOS) and also overlap population density of state (COOP or OPDOS) diagrams analysis were presented. The dipole moment, linear polarizability and first order hyperpolarizability values were also computed. The linear polarizability and first order hyperpolarizabilities of the studied molecule indicate that the compound is a good candidate for nonlinear optical materials.

Development of a canine model to enable the preclinical assessment of pH-dependent absorption of test compounds.

PubMed

Fancher, R Marcus; Zhang, Hongjian; Sleczka, Bogdan; Derbin, George; Rockar, Richard; Marathe, Punit

2011-07-01

A preclinical canine model capable of predicting a compound's potential for pH-dependent absorption in humans was developed. This involved the surgical insertion of a gastrostomy feeding tube into the stomach of a beagle dog. The tube was sutured in position to allow frequent withdrawal of gastric fluid for pH measurement. Therefore, it was possible to measure pH in the stomach and assess the effect of gastric pH-modifying agents on the absorption of various test compounds. Fasted gastric pH in the dog showed considerable inter- and intra-animal variability. Pretreatment of pentagastrin (6 µg/kg intramuscularly) 20 min prior to test compound administration was determined to be adequate for simulating fasting stomach pH in humans. Pretreatment with famotidine [40 mg orally] 1 h prior to test compound administration was determined to be adequate for simulating human gastric pH when acid-reducing agents are coadministered. Pentagastrin and famotidine pretreatments were used to test two discovery compounds and distinct differences in their potential for pH-dependent absorption were observed. The model described herein can be used preclinically to screen out compounds, differentiate compounds, and support the assessment of various formulation- and prodrug-based strategies to mitigate the pH effect. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

Metformin Is a Substrate and Inhibitor of the Human Thiamine Transporter, THTR-2 (SLC19A3).

PubMed

Liang, Xiaomin; Chien, Huan-Chieh; Yee, Sook Wah; Giacomini, Marilyn M; Chen, Eugene C; Piao, Meiling; Hao, Jia; Twelves, Jolyn; Lepist, Eve-Irene; Ray, Adrian S; Giacomini, Kathleen M

2015-12-07

The biguanide metformin is widely used as first-line therapy for the treatment of type 2 diabetes. Predominately a cation at physiological pH's, metformin is transported by membrane transporters, which play major roles in its absorption and disposition. Recently, our laboratory demonstrated that organic cation transporter 1, OCT1, the major hepatic uptake transporter for metformin, was also the primary hepatic uptake transporter for thiamine, vitamin B1. In this study, we tested the reverse, i.e., that metformin is a substrate of thiamine transporters (THTR-1, SLC19A2, and THTR-2, SLC19A3). Our study demonstrated that human THTR-2 (hTHTR-2), SLC19A3, which is highly expressed in the small intestine, but not hTHTR-1, transports metformin (Km = 1.15 ± 0.2 mM) and other cationic compounds (MPP(+) and famotidine). The uptake mechanism for hTHTR-2 was pH and electrochemical gradient sensitive. Furthermore, metformin as well as other drugs including phenformin, chloroquine, verapamil, famotidine, and amprolium inhibited hTHTR-2 mediated uptake of both thiamine and metformin. Species differences in the substrate specificity of THTR-2 between human and mouse orthologues were observed. Taken together, our data suggest that hTHTR-2 may play a role in the intestinal absorption and tissue distribution of metformin and other organic cations and that the transporter may be a target for drug-drug and drug-nutrient interactions.

Recent developments of 2-aminothiazoles in medicinal chemistry.

PubMed

Das, Debasis; Sikdar, Papiya; Bairagi, Moumita

2016-02-15

The 2-aminothiazole (2-AT) core is an active pharmacophore and used in medicinal chemistry and drug discovery research. A number of drugs with 2-AT core are in the market, e.g. Famotidine, Cefdinir, Meloxcam etc. Recently, 2-AT core has been explored for many more important therapeutic areas and identified new 2-aminothiazoles with anticancer, antitumor, antidiebatic and anticonvulsant activity. In this review, we discuss the newly identified and developed 2-aminothiazoles in recent years and their use in medicinal chemistry and pharmacology. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Comparative study of therapeutic effects of PPI and H2RA on ulcers during continuous aspirin therapy

PubMed Central

Nema, Hiroaki; Kato, Mototsugu

2010-01-01

AIM: To compare the therapeutic effects of proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) on gastroduodenal ulcers under continuous use of low-dose aspirin. METHODS: Sixty patients who had a gastroduodenal ulcer on screening endoscopy but required continuous use of low-dose aspirin were randomly assigned to receive PPI (lansoprazole 30 mg, n = 30) or H2RA (famotidine 40 mg or if famotidine had been administered before assignment, ranitidine 300 mg, n = 30). The therapeutic effects were evaluated by endoscopy after 8-wk treatment. The presence or absence of Helicobacter pylori (H. pylori) was determined by urea breath test before treatment. Abdominal symptoms were compared with the gastrointestinal symptom rating scale (GSRS) questionnaire before and after treatment. RESULTS: Twenty-six patients in the PPI group and 26 patients in the H2RA group, excluding dropouts, were analyzed. There were no significant differences in median age, sex, underlying disease, smoking status, H. pylori infection, prevalence of ulcers before treatment, and lesion site between the two groups. The therapeutic effects were endoscopically evaluated as healed in 23 patients (88.5%) and not healed in 3 patients in the PPI group and as healed in 22 patients (84.6%) and not healed in 4 patients in the H2RA group. Abdominal symptoms before treatment were uncommon in both groups; the GSRS scores were not significantly reduced after treatment as compared with before treatment. CONCLUSION: The healing rate of gastroduodenal ulcers during continuous use of low-dose aspirin was greater than 80% in both the PPI group and the H2RA group, with no significant difference between the two groups. PMID:21072898

Evidence of anti-oxidant role of sucralfate in gastric mucosal protection.

PubMed

Laudanno, O M; Bedini, O A; Cesolari, J A; San Miguel, P

1990-02-01

Six percent hydrogen peroxide (H2O2) was used as a generator of the *OH free radical, and as an aggressor of gastric mucosa, in 100 Wistar rats. The mucosal cytoprotector effect of sucralfate, misoprostol, enprostil, cimetidine, ranitidine, famotidine and 10% aluminum sulphate yielded almost complete macroscopic and histological protection to the gastric mucosa. Misoprostol or enprostil gave partial protection whereas the H2 blockers aggravated the gastric necrotic lesions produced by the H2O2. We conclude that sucralfate is a true anti-oxidant that protects the gastric mucosa through its aluminum and sulphydril components, the increment of gastric mucins and endogenous PGs.

Protective effect of lafutidine, a histamine H2 receptor antagonist, against loxoprofen-induced small intestinal lesions in rats.

PubMed

Amagase, Kikuko; Ochi, Akimu; Sugihara, Tetsuya; Kato, Shinichi; Takeuchi, Koji

2010-05-01

We examined the effect of lafutidine, a histamine H(2) receptor antagonist with a mucosal protective action mediated by capsaicin-sensitive sensory neurons (CSN), on intestinal lesions produced by loxoprofen administration in rats. Animals were given loxoprofen (10-100 mg/kg p.o.) and killed 24 h later. Lafutidine (10 and 30 mg/kg), cimetidine (100 mg/kg) or famotidine (30 mg/kg) was given twice p.o. at 0.5 h before and 6 h after loxoprofen. Omeprazole (100 mg/kg) was given p.o. once 0.5 h before. Ampicillin (800 mg/kg) was given p.o. twice at 24 h and 0.5 h before loxoprofen, while 16,16-dimethyl prostaglandin E(2) (dmPGE(2); 0.01 mg/kg) was given i.v. twice at 5 min before and 6 h after. Loxoprofen dose-dependently produced hemorrhagic lesions in the small intestine, accompanied by invasion of enterobacteria and increased inducible nitric oxide synthase (iNOS) expression as well as myeloperoxidase activity in the mucosa. The ulcerogenic response to loxoprofen (60 mg/kg) was significantly prevented by lafutidine (30 mg/kg), similar to dmPGE(2) and ampicillin, and the effect of lafutidine was totally attenuated by ablation of CSN. Neither cimetidine, famotidine nor omeprazole had a significant effect against these lesions. Lafutidine alone increased mucus secretion and reverted the decreased mucus response to loxoprofen, resulting in suppression of bacterial invasion and iNOS expression. In addition, loxoprofen downregulated Muc2 expression, and this response was totally reversed by lafutidine mediated by CSN. Lafutidine protects the small intestine against loxoprofen-induced lesions, essentially mediated by the CSN, and this effect may be functionally associated with increased Muc2 expression/mucus secretion, an important factor in the suppression of bacterial invasion.

Shifting physician prescribing to a preferred histamine-2-receptor antagonist. Effects of a multifactorial intervention in a mixed-model health maintenance organization.

PubMed

Brufsky, J W; Ross-Degnan, D; Calabrese, D; Gao, X; Soumerai, S B

1998-03-01

This study was undertaken to determine whether a program of education, therapeutic reevaluation of eligible patients, and performance feedback could shift prescribing to cimetidine from other histamine-2 receptor antagonists, which commonly are used in the management of ulcers and reflux, and reduce costs without increasing rates of ulcer-related hospital admissions. This study used an interrupted monthly time series with comparison series in a large mixed-model health maintenance organization. Physicians employed in health centers (staff model) and physicians in independent medical groups contracting to provide health maintenance organization services (group model) participated. The comparative percentage prescribed of specific histamine-2 receptor antagonists (market share), total histamine-2 receptor antagonist prescribing, cost per histamine-2 receptor antagonist prescription, and the rate of hospitalization for gastrointestinal illness were assessed. In the staff model, therapeutic reevaluation resulted in a sudden increase in market share of the preferred histamine-2 receptor antagonist cimetidine (+53.8%) and a sudden decrease in ranitidine (-44.7%) and famotidine (-4.8%); subsequently, cimetidine market share grew by 1.1% per month. In the group model, therapeutic reevaluation resulted in increased cimetidine market share (+9.7%) and decreased prescribing of other histamine-2 receptor antagonists (ranitidine -11.6%; famotidine -1.2%). Performance feedback did not result in further changes in prescribing in either setting. Use of omeprazole, an expensive alternative, essentially was unchanged by the interventions, as were overall histamine-2 receptor antagonist prescribing and hospital admissions for gastrointestinal illnesses. This intervention, which cost approximately $60,000 to implement, resulted in estimated annual savings in histamine-2 receptor antagonist expenditures of $1.06 million. Annual savings in histamine-2 receptor antagonist expenditures

pH-metric solubility. 2: correlation between the acid-base titration and the saturation shake-flask solubility-pH methods.

PubMed

Avdeef, A; Berger, C M; Brownell, C

2000-01-01

The objective of this study was to compare the results of a normal saturation shake-flask method to a new potentiometric acid-base titration method for determining the intrinsic solubility and the solubility-pH profiles of ionizable molecules, and to report the solubility constants determined by the latter technique. The solubility-pH profiles of twelve generic drugs (atenolol, diclofenac.Na, famotidine, flurbiprofen, furosemide, hydrochlorothiazide, ibuprofen, ketoprofen, labetolol.HCl, naproxen, phenytoin, and propranolol.HCl), with solubilities spanning over six orders of magnitude, were determined both by the new pH-metric method and by a traditional approach (24 hr shaking of saturated solutions, followed by filtration, then HPLC assaying with UV detection). The 212 separate saturation shake-flask solubility measurements and those derived from 65 potentiometric titrations agreed well. The analysis produced the correlation equation: log(1/S)titration = -0.063(+/- 0.032) + 1.025(+/- 0.011) log(1/S)shake-flask, s = 0.20, r2 = 0.978. The potentiometrically-derived intrinsic solubilities of the drugs were: atenolol 13.5 mg/mL, diclofenac.Na 0.82 microg/mL, famotidine 1.1 mg/ mL, flurbiprofen 10.6 microg/mL, furosemide 5.9 microg/mL, hydrochlorothiazide 0.70 mg/mL, ibuprofen 49 microg/mL, ketoprofen 118 microg/mL, labetolol.HCl 128 microg/mL, naproxen 14 microg/mL, phenytoin 19 microg/mL, and propranolol.HCl 70 microg/mL. The new potentiometric method was shown to be reliable for determining the solubility-pH profiles of uncharged ionizable drug substances. Its speed compared to conventional equilibrium measurements, its sound theoretical basis, its ability to generate the full solubility-pH profile from a single titration, and its dynamic range (currently estimated to be seven orders of magnitude) make the new pH-metric method an attractive addition to traditional approaches used by preformulation and development scientists. It may be useful even to discovery

A screen of pharmaceutical drugs for their ability to cause short-term morbidity and mortality in the common bed bug, Cimex lectularius L.

PubMed

Sheele, Johnathan M; Ridge, Gale E; Du, Wenjing; Mallipeddi, Nikhil; Vallabhaneni, Mayur

2017-10-01

The common bed bug, Cimex lectularius L., is a hematophagous ectoparasite that preferentially feeds on humans. Pharmaceuticals present in a person's blood may adversely affect C. lectularius when it feeds. We fed >10,000 C. lectularius on blood samples containing more than 400 different drug doses and drug combinations using an in vitro feeding system to determine insect mortality. The majority of drug doses approximated the peak plasma concentration in humans taking those drugs. Twenty-one drugs were found to cause >17% 12-14-day mortality compared to 8.5% mortality in the control (p < 0.05), but postliminary testing of three of the drugs, famotidine, ethambutol, and primaquine, did not demonstrate an increase in C. lectularius mortality. We also tested 23 drugs for their effects on C. lectularius fecundity. The results may have implications for understanding C. lectularius population dynamics in an infestation.

The use of H2 antagonists in treating and preventing NSAID-induced mucosal damage.

PubMed

Tuskey, Anne; Peura, David

2013-01-01

Pain affects the quality of life for millions of individuals and is a major reason for healthcare utilization. As populations age, medical personnel will need to manage more and more patients suffering from pain associated with degenerative and inflammatory musculoskeletal disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective treatment for both acute and chronic musculoskeletal pain; however, their use is associated with potentially significant gastrointestinal (GI) toxicity. Guidelines suggest various strategies to prevent problems in those at risk for NSAID-associated GI complications. In this article, we review the data supporting one such strategy - the use of histamine type-2 receptor antagonists (H2RAs) - for the prevention of GI adverse events in NSAID users. Older studies suggest that high-dose H2RAs are effective in preventing upper GI ulcers and dyspepsia. This suggestion was recently confirmed during clinical trials with a new ibuprofen/famotidine combination that reduced the risk of ulcers by 50% compared with ibuprofen alone.

The use of H2 antagonists in treating and preventing NSAID-induced mucosal damage

PubMed Central

2013-01-01

Pain affects the quality of life for millions of individuals and is a major reason for healthcare utilization. As populations age, medical personnel will need to manage more and more patients suffering from pain associated with degenerative and inflammatory musculoskeletal disorders. Nonsteroidal anti-inflammatory drugs (NSAIDs) are an effective treatment for both acute and chronic musculoskeletal pain; however, their use is associated with potentially significant gastrointestinal (GI) toxicity. Guidelines suggest various strategies to prevent problems in those at risk for NSAID-associated GI complications. In this article, we review the data supporting one such strategy - the use of histamine type-2 receptor antagonists (H2RAs) - for the prevention of GI adverse events in NSAID users. Older studies suggest that high-dose H2RAs are effective in preventing upper GI ulcers and dyspepsia. This suggestion was recently confirmed during clinical trials with a new ibuprofen/famotidine combination that reduced the risk of ulcers by 50% compared with ibuprofen alone. PMID:24267478

Ion mobility spectrometry for the rapid analysis of over-the-counter drugs and beverages

PubMed Central

Fernández-Maestre, Roberto

2009-01-01

In the pharmaceutical industry, there are increasing requirements for analytical methods in quality assessment for the production of drugs. In this investigation, ion mobility spectrometry (IMS) was used for the rapid qualitative separation and identification of active ingredients in generic over-the-counter drugs and food additives in beverages. The active ingredients determined in drugs were acetaminophen, aspartame, bisacodyl, caffeine, dextromethorphan, diphenhydramine, famotidine, glucosamine, guaifenesin, loratadine, niacin, phenylephrine, pyridoxine, thiamin, and tetrahydrozoline. Aspartame and caffeine were determined in beverages. Fourteen over-the-counter drugs and beverages were analyzed. Analysis times below 10 s were obtained for IMS, and reduced mobilities were reported for the first time for 12 compounds. A quadrupole mass spectrometer coupled to a mobility spectrometer was used to assure a correct peak assignation. The combination of fast analysis, low cost, and inexpensive maintenance of IMS instruments makes IMS an attractive technique for the qualitative determination of the active ingredients in over-the-counter drugs and food additives in manufacture quality control and cleaning verification for the drug and food industries. PMID:20835390

[Case of general anesthesia combined with epidural anesthesia in a pregnant woman undergoing thoracotomy for spontaneous pneumothorax].

PubMed

Mitsunari, Hiroaki; Yamagata, Katsuyuki; Sakuma, Shiori

2008-02-01

General anesthesia combined with epidural anesthesia for thoracotomy due to spontaneous pneumothorax was given to a pregnant woman at 21st week of gestation. She was premedicated intravenously with famotidine 20 mg and metoclopramide 10 mg. Mepivacaine 1% was administered through a thoracic epidural catheter. General anesthesia was induced by thiamylal 225 mg, vecuronium 8 mg and fentanyl 100 mcg, and maintained by sevoflurane, vecuronium and fentanyl. Endobronchial intubation with a 35Fr Bronchocath double-lumen tube was successful and one-lung ventilation was commenced to maintain the end-expiratory CO2 pressure at 30 to 35 mmHg with Sp(O2) remaining 100%. Ephedrine 16mg (in 4mg increments) was required to maintain systolic blood pressure above 100 mmHg. After the surgery, ropivacaine 0.2% was administered through the catheter. There were no clinical signs of fetal distress during the perioperative period. Postoperative pregnancy and delivery were uneventful. We succeeded in the anesthetic management by avoiding hypoxia, hypercapnia, hypocapnia and hypotension during the surgery.

Immediate hypersensitivity reaction associated with the rapid infusion of Crotalidae polyvalent immune Fab (ovine).

PubMed

Holstege, Christopher P; Wu, Jeffrey; Baer, Alexander B

2002-06-01

A 16-year-old boy presented to the emergency department with rapidly progressing extremity pain, edema, and ecchymosis after envenomation by a copperhead. Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) was infused. Six vials were placed in 250 mL of normal saline solution, and the infusion was gradually increased. Fifty minutes after beginning, the infusion was increased to 640 mL/h. Within minutes of the rate increase, the patient experienced full-body urticaria, facial edema, voice change, and tachycardia. The infusion was stopped. Hydroxyzine pamoate, famotidine, methylprednisolone, and a 1-L bolus of normal saline solution were administered intravenously. The symptoms abated, and the remaining FabAV was infused at a slower rate without return of this reaction. This immediate hypersensitivity reaction was most likely a rate-related anaphylactoid reaction that has not been previously reported with FabAV.[Holstege CP, Wu J, Baer AB. Immediate hypersensitivity reaction associated with the rapid infusion of Crotalidae polyvalent immune Fab (ovine). Ann Emerg Med. June 2002;39:677-679.

Ranitidine-Associated Sleep Disturbance: Case Report and Review of H2 Antihistamine-Related Central Nervous System Adverse Effects.

PubMed

Werbel, Tyler; Cohen, Philip R

2018-04-03

Ranitidine is an H2 antihistamine used as an off-label therapy for recalcitrant verruca vulgaris. We describe a man who developed a sleep disturbance after initiating therapy with ranitidine and review similar adverse effects associated with other drugs in this class. The patient was a 40-year-old man with an eight-year history of a wart on his right plantar foot that was recalcitrant to several topical therapies. Adjunctive treatment with ranitidine 150 mg twice daily was initiated. He developed sleep disturbance with bizarre dreams and gastrointestinal symptoms. All symptoms resolved after discontinuation of the medication and recurred when he restarted the drug. PubMed was searched for the following terms: disturbance, dream, ranitidine, verruca, wart, and Zantac. The papers containing these terms and their references were reviewed. Sleep disturbance caused by ranitidine is an uncommon adverse event in patients receiving the drug. However, similar reactions have been observed with other H2 antihistamines such as cimetidine and famotidine. Clinicians should be aware that sleep disturbance secondary to ranitidine is a potential side effect of this medication.

Topical flurbiprofen toxicosis in a cat.

PubMed

Yi, Elizabeth M; Leech, Elizabeth

2017-11-01

To describe the clinical presentation and treatment of a cat with flurbiprofen toxicosis due to topical cream exposure. A 3-year-old castrated male domestic shorthair cat presented to an emergency and referral center for acute lethargy, hematemesis, and anemia. Severe azotemia was observed on serum biochemistry panel. The patient's anemia was treated with packed RBC transfusion, and treatment with crystalloid fluids, famotidine, pantoprazole, ampicillin, and sucralfate were begun on presentation. Anemia became intractable and the patient received multiple packed RBC and whole blood transfusions. Severe gastric ulcerations and duodenal perforation were confirmed via gastroduodenoscopy, and the patient was treated with surgical excision and repair of duodenal perforation. Azotemia resolved with IV fluid therapy, and anemia resolved following surgery. The patient recovered and was discharged after 9 days of hospitalization. The patient had likely been exposed to the owner's compounded pain relief cream containing 10% flurbiprofen. There was confirmation of flurbiprofen exposure via acid extraction urine analysis at a university toxicology laboratory. This is the first described case of flurbiprofen toxicosis due to topical cream exposure in a cat. © Veterinary Emergency and Critical Care Society 2017.

Design of an expert system for the development and formulation of push-pull osmotic pump tablets containing poorly water-soluble drugs.

PubMed

Zhang, Zhi-hong; Dong, Hong-ye; Peng, Bo; Liu, Hong-fei; Li, Chun-lei; Liang, Min; Pan, Wei-san

2011-05-30

The purpose of this article was to build an expert system for the development and formulation of push-pull osmotic pump tablets (PPOP). Hundreds of PPOP formulations were studied according to different poorly water-soluble drugs and pharmaceutical acceptable excipients. The knowledge base including database and rule base was built based on the reported results of hundreds of PPOP formulations containing different poorly water-soluble drugs and pharmaceutical excipients and the experiences available from other researchers. The prediction model of release behavior was built using back propagation (BP) neural network, which is good at nonlinear mapping and learning function. Formulation design model was established based on the prediction model of release behavior, which was the nucleus of the inference engine. Finally, the expert system program was constructed by VB.NET associating with SQL Server. Expert system is one of the most popular aspects in artificial intelligence. To date there is no expert system available for the formulation of controlled release dosage forms yet. Moreover, osmotic pump technology (OPT) is gradually getting consummate all over the world. It is meaningful to apply expert system on OPT. Famotidine, a water insoluble drug was chosen as the model drug to validate the applicability of the developed expert system. Copyright © 2011 Elsevier B.V. All rights reserved.

Statistical optimization and fabrication of a press coated pulsatile dosage form to treat nocturnal acid breakthrough.

PubMed

Agarwal, Vaibhav; Bansal, Mayank

2013-08-01

Present work focuses on the use of mimosa seed gum to develop a drug delivery system making combined use of floating and pulsatile principles, for the chrono-prevention of nocturnal acid breakthrough. The desired aim was achieved by fabricating a floating delivery system bearing time - lagged coating of Mimosa pudica seed polymer for the programmed release of Famotidine. Response Surface Methodology was the statistical tool that was employed for experiment designing, mathematical model generation and optimization study. A 3(2) full factorial design was used in designing the experiment.% weight ratio of mimosa gum to hydroxy propyl methyl cellulose in the coating combination and the coating weight were the independent variables, whereas the lag time and the cumulative % drug release in 360 minutes were the observed responses. Results revealed that both the coating composition and the coating weight significantly affected the release of drug from the dosage form. The optimized formulation prepared according to the computer generated software, Design-Expert(®) deciphered response which were in close proximity with the experimental responses, thus confirming the robustness as well as accuracy of the predicted model for the utilization of natural polymer like mimosa seed gum for the chronotherapeutic treatment of nocturnal acid breakthrough.

Facile synthesis of functionalized ionic surfactant templated mesoporous silica for incorporation of poorly water-soluble drug.

PubMed

Li, Jing; Xu, Lu; Yang, Baixue; Wang, Hongyu; Bao, Zhihong; Pan, Weisan; Li, Sanming

2015-08-15

The present paper reported amino group functionalized anionic surfactant templated mesoporous silica (Amino-AMS) for loading and release of poorly water-soluble drug indomethacin (IMC) and carboxyl group functionalized cationic surfactant templated mesoporous silica (Carboxyl-CMS) for loading and release of poorly water-soluble drug famotidine (FMT). Herein, Amino-AMS and Carboxyl-CMS were facilely synthesized using co-condensation method through two types of silane coupling agent. Amino-AMS was spherical nanoparticles, and Carboxyl-CMS was well-formed spherical nanosphere with a thin layer presented at the edge. Drug loading capacity was obviously enhanced when using Amino-AMS and Carboxyl-CMS as drug carriers due to the stronger hydrogen bonding force formed between surface modified carrier and drug. Amino-AMS and Carboxyl-CMS had the ability to transform crystalline state of loaded drug from crystalline phase to amorphous phase. Therefore, IMC loaded Amino-AMS presented obviously faster release than IMC because amorphous phase of IMC favored its dissolution. The application of asymmetric membrane capsule delayed FMT release significantly, and Carboxyl-CMS favored sustained release of FMT due to its long mesoporous channels and strong interaction formed between its carboxyl group and amino group of FMT. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhanced Sensitivity to Detection Nanomolar Level of Cu2 + Compared to Spectrophotometry Method by Functionalized Gold Nanoparticles: Design of Sensor Assisted by Exploiting First-order Data with Chemometrics

NASA Astrophysics Data System (ADS)

Rasouli, Zolaikha; Ghavami, Raouf

2018-02-01

A simple, sensitive and efficient colorimetric assay platform for the determination of Cu2 + was proposed with the aim of developing sensitive detection based on the aggregation of AuNPs in presence of a histamine H2-receptor antagonist (famotidine, FAM) as recognition site. This study is the first to demonstrate that the molar extinction coefficients of the complexes formed by FAM and Cu2 + are very low (by analyzing the chemometrics methods on the first order data arising from different metal to ligand ratio method), leading to the undesirable sensitivity of FAM-based assays. To resolve the problem of low sensitivity, the colorimetry method based on the Cu2 +-induced aggregation of AuNPs functionalized with FAM was introduced. This procedure is accompanied by a color change from bright red to blue which can be observed with the naked eyes. Detection sensitivity obtained by the developed method increased about 100 fold compared with the spectrophotometry method. This sensor exhibited a good linear relation between the absorbance ratios at 670 to 520 nm (A670/520) and the concentration in the range 2-110 nM with LOD = 0.76 nM. The satisfactory analytical performance of the proposed sensor facilitates the development of simple and affordable UV-Vis chemosensors for environmental applications.

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.

[Adverse effects of non-steroidal anti-inflammatory drugs. A prevalence study in Austria].

PubMed

Kolarz, Gernot; Mayrhofer, Franz; Neumann, Kurt; Singer, Franz

2003-01-31

Gastrointestinal side effects are the limiting factor in the prescription of non-steroidal antirheumatic drugs (NSAID). However, there are no recent data from Austria. The aim of this prevalence study was therefore to assess the gastrointestinal risk from NSAID in Austria. A total of 1347 patients were observed in an outpatient setting between March 2000 and February 2001. Side effects from NSAID were documented by questionnaire at two time points with a mean interval of 31 days. Documented data were analysed descriptively using an explorative strategy. The prevalence of side effects was compared to data from literature. Side effects were reported by 18.1% of the patients, severe gastro-intestinal complications (ulcer, bleeding, perforation) were diagnosed in 0.7%. Prescription of effective GI-protection (proton pump inhibitors, misoprostole, famotidin in high dose) was seen in only one third of the patients at risk. The prevalence of severe gastrointestinal side effects by NSAIDs assessed in our study was clearly lower than the prevalence reported in the Anglo-American literature. This may be due to a different prescription behaviour: about 75% of the patients took Diclofenac, lbuprofen or Meloxicam, drugs which have a very low potential of gastrointestinal complications. However, more information for general practitioners is needed yet to sufficiently protect patients at gastrointestinal risk from NSAID.

In vitro study of histamine and histamine receptor ligands influence on the adhesion of purified human eosinophils to endothelium.

PubMed

Grosicki, Marek; Wójcik, Tomasz; Chlopicki, Stefan; Kieć-Kononowicz, Katarzyna

2016-04-15

It is a well-known fact that histamine is involved in eosinophil-dependent inflammatory responses including cellular chemotaxis and migration. Nevertheless, the relative role of histamine receptors in the mechanisms of eosinophils adhesion to endothelial cells is not known. Therefore the aim of presented study was to examine the effect of selective histamine receptors ligands on eosinophils adhesion to endothelium. For that purpose the highly purified human eosinophils have been isolated from the peripheral blood. The viability and functional integrity of isolated eosinophils have been validated in several tests. Histamine as well as 4-methylhistamine (selective H4 agonist) in concentration-dependent manner significantly increased number of eosinophils that adhere to endothelium. Among the selective histamine receptors antagonist or H1 inverse agonist only JNJ7777120 (histamine H4 antagonist) and thioperamide (dual histamine H3/H4 antagonist) had direct effect on eosinophils adhesion to endothelial cells. Antagonists of H1 (diphenhydramine, mepyramine) H2 (ranitidine and famotidine) and H3 (pitolisant) histamine receptors were ineffective. To the best of our knowledge, this is the first study to demonstrate that histamine receptor H4 plays a dominant role in histamine-induced eosinophils adhesion to endothelium. Copyright © 2016 Elsevier B.V. All rights reserved.

Gastrointestinal medications and breastfeeding.

PubMed

Hagemann, T M

1998-09-01

Medications used to treat gastrointestinal symptoms are increasingly being used as more have been gained nonprescription status. Most of the gastrointestinal medications, such as laxatives, antacids, and antidiarrheal agents, are used short term. Women who breastfeed should be aware of the risks of taking any medications, whether prescription or nonprescription. There is little information describing transfer into breast milk for many of these products. Cimetidine, atropine, cascara, cisapride, loperamide, magnesium sulfate, and senna are the only products identified by the AAP as compatible with breast feeding. Metoclopramide is listed by the AAP as a drug whose effect on nursing infants is unknown but may be of potential concern, although studies published to date have not reported any adverse effects. The safest laxatives and antidiarrheals are those that are not absorbed and should be considered first-line therapy for conditions of constipation or loose stools. Famotidine and nizatidine are excreted into breast milk to a lesser extent than cimetidine or ranitidine and may be the preferred histamine antagonists. Despite the limited data on the use of cisapride in nursing women, it is considered safe by the AAP and may be preferred over metoclopramide for first-line prescription treatment of heartburn. Although most of these agents appear safe in the nursing infant, caretakers should be aware of the potential adverse reactions that may occur in infants whose mothers require these products.

Acute hypersensitivity reaction to Crotalidae polyvalent immune Fab (CroFab) as initial presentation of galactose-α-1,3-galactose (α-gal) allergy.

PubMed

Rizer, Justin; Brill, Kaitlin; Charlton, Nathan; King, Joshua

2017-08-01

Crotalidae polyvalent immune Fab antivenom (CroFab), commonly used for the treatment of clinically significant North American crotalinae envenomation, is generally well-tolerated. A novel form of anaphylaxis due to an IgE antibody response to the mammalian oligosaccharide galactose-α-1,3-galactose (α-gal) has been established following red-meat consumption as well as IV administration of cetuximab, which contain the α-gal epitope. We present a case of α-gal allergy discovered after acute hypersensitivity reaction to FabAV. A 61-year-old healthy female was bitten on her left ankle by Agkistrodon contortrix. Given the patient's rapid progression of pain and swelling, she was given FabAV. During infusion of FabAV, she developed diffuse hives over her entire body and itching, but denied respiratory or gastrointestinal symptoms and her vital signs remained stable. The FabAV was immediately discontinued and she received intravenous diphenhydramine and famotidine with gradual resolution of symptoms. On further discussion, she denied a history of α-gal or papaya allergy but rarely ate red meat and endorsed sustaining frequent tick bites. Subsequent antibody testing was significant for an α-1,3-galactose IgE concentration of 45,000 U/L (normal <3500 U/L), confirming α-gal allergy. To our knowledge, this is the first report of FabAV hypersensitivity associated with an underlying α-gal allergy.

Investigation of antiulcer and antioxidant activity of moclobemide in rats.

PubMed

Albayrak, Abdulmecit; Alp, Hamit H; Suleyman, Halis

2015-02-01

Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. Moclobemide is an antidepressant drug which inhibits monoamine oxidase-A (MAO) enzyme selectively. When it is compared to the classic antidepressants drugs, moclobemide is the first choice in depression treatment because of its effectiveness and less side effects. This study aimed to investigate the antiulcer effects of moclobemide and to determine its relationship with antioxidant mechanisms in rat gastric tissue. The antiulcer activities of 10, 20, 40, 80, 150 mg/kg moclobemide and 20 mg/kg famotidine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Moclobemide decreased the indomethacin-induced ulcers significantly at all doses used. While used doses of moclobemide increased the glutathione (GSH), nitric oxide (NO) level and superoxide dismutase (SOD) activity, it decreased the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in stomach tissue when compared to the control group. It is determined that an antidepressant drug, moclobemide is a potent anti-ulcer agent. Inhibition of toxic oxidant radicals and activation of antioxidant mechanisms play a role in its anti-ulcer effect mechanisms.

Antiulcerogenic Effect of Gallic Acid in Rats and its Effect on Oxidant and Antioxidant Parameters in Stomach Tissue

PubMed Central

Sen, S.; Asokkumar, K.; Umamaheswari, M.; Sivashanmugam, A. T.; Subhadradevi, V.

2013-01-01

In the present study, we investigate the antiulcerogenic effect of gallic acid against aspirin plus pyrolus ligation-induced gastric ulcer in rats. Rats were treated with gallic acid (100 and 200 mg/kg) and famotidine (20 mg/kg) for 1 week, followed by induction of gastric ulcer using the aspirin plus pyrolus ligation model. At the end of 4 h after ligation, the rats were sacrificed and ulcer index, gastric juice volume, pH and other biochemical parameter of gastric juice were evaluated. Stomachs of rats were evaluated biochemically to determine oxidant and antioxidant parameters. Pretreatment with gallic acid significantly decreased ulcer index, gastric juice volume, free and total acidity, total protein, DNA content and increased pH and carbohydrates concentration. Gallic acid at a dose of 100 and 200 mg/kg exerted 69.7 and 78.9% ulcer inhibition, respectively. The levels of superoxide dismutase, catalase, reduced glutathione, glutathione reductase, glutathione peroxidise, glucose-6-phosphate dehydrogenase were increased while reduction in myeloperoxidase and lipid peroxidation were observed in the stomach tissues of the drug treated rats. The histopathological studies further confirmed the antiulcer activity of gallic acid. We conclude that the gallic acid possesses antiulcer effect and that these occur by a mechanism that involves attenuation of offensive factors, improvement of mucosal defensive with activation of antioxidant parameters and inhibition of some toxic oxidant parameters. PMID:24019562

Pharmacological management of persistent hostility and aggression in persons with schizophrenia spectrum disorders: a systematic review.

PubMed

Victoroff, Jeff; Coburn, Kerry; Reeve, Alya; Sampson, Shirlene; Shillcutt, Samuel

2014-01-01

The incidence of aggressive behaviors is higher among persons with schizophrenia spectrum disorders (SSDs) than among persons without such disorders. This phenomenon represents a risk to the well-being of patients, their families, and society. The authors undertook a systematic review of the English language literature to determine the efficacy of neuropharmacological agents for the management of hostility and aggression among persons with SSDs. The search combined findings from the Medline, EMBASE, and PsycINFO databases. Ninety-two full text articles were identified that reported relevant findings. The American Academy of Neurology criteria were used to determine levels of evidence. Paliperidone-extended release is probably effective for the management of hostility among inpatients with SSDs who have not been preselected for aggression (Level B). Clozapine is possibly more effective than haloperidol for the management of overt aggression and possibly more effective than chlorpromazine for the management of hostility among inpatients with SSDs who have not been preselected for aggression (Level C). Clozapine is also possibly more effective than olanzapine or haloperidol for reducing aggression among selected physically assaultive inpatients (Level C). Adjunctive propranolol, valproic acid, and famotidine are possibly effective for reducing some aspects of hostility or aggression among inpatients with SSDs (Level C). Paliperidone-extended release currently appears to be the agent for the management of hostility among inpatients with SSDs for which there is the strongest evidence of efficacy.

Formulation and optimisation of raft-forming chewable tablets containing H2 antagonist.

PubMed

Prajapati, Shailesh T; Mehta, Anant P; Modhia, Ishan P; Patel, Chhagan N

2012-10-01

The purpose of this research work was to formulate raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent. Tablets were prepared by wet granulation and evaluated for raft strength, acid neutralisation capacity, weight variation, % drug content, thickness, hardness, friability and in vitro drug release. Various raft-forming agents were used in preliminary screening. A 2(3) full-factorial design was used in the present study for optimisation. The amount of sodium alginate, amount of calcium carbonate and amount sodium bicarbonate were selected as independent variables. Raft strength, acid neutralisation capacity and drug release at 30 min were selected as responses. Tablets containing sodium alginate were having maximum raft strength as compared with other raft-forming agents. Acid neutralisation capacity and in vitro drug release of all factorial batches were found to be satisfactory. The F5 batch was optimised based on maximum raft strength and good acid neutralisation capacity. Drug-excipient compatibility study showed no interaction between the drug and excipients. Stability study of the optimised formulation showed that the tablets were stable at accelerated environmental conditions. It was concluded that raft-forming chewable tablets prepared using an optimum amount of sodium alginate, calcium carbonate and sodium bicarbonate could be an efficient dosage form in the treatment of gastro oesophageal reflux disease.

Triple antimicrobial therapy and acid suppression in dogs with chronic vomiting and gastric Helicobacter spp.

PubMed

Leib, Michael S; Duncan, Robert B; Ward, Daniel L

2007-01-01

Helicobacter pylori is a common cause of gastritis and peptic ulcers in humans. Many dogs, including those with gastritis and chronic vomiting, are infected with Helicobacter spp. Triple antimicrobial therapy will eradicate Helicobacter infection, improve gastritis, and reduce clinical signs. The addition of acid suppression medication will not improve results. Twenty-four pet dogs with chronic vomiting and gastric Helicobacter spp. Dogs were randomly assigned to triple antimicrobial therapy with or without famotidine. Gastroduodenoscopy was performed 4 weeks and 6 months after therapy. Helicobacter spp status was determined by histologic assessment of gastric mucosal biopsy specimens. Eradication rates for each treatment were not significantly different and combined were 75 and 42.9% at 4 weeks and 6 months, respectively. A greater improvement in gastritis scores occurred in dogs that became Helicobacter spp negative. Overall, the frequency of vomiting was reduced by 86.4%, but there were no differences between treatments. Eradication rates of Helicobacter spp with both treatments were not significantly different. Eradication rates at 6 months were modest, and more effective treatments should be developed. Acid suppression is not a necessary component of treatment protocols for dogs. Eradication of gastric Helicobacter spp was associated with improvement in gastritis scores. Dramatic reduction of the vomiting frequency occurred with both treatment protocols. Gastric Helicobacter spp may cause or contribute to chronic vomiting and gastritis in some dogs.

Therapeutic Options for Controlling Fluids in the Visual System

NASA Technical Reports Server (NTRS)

Curry, Kristina M.; Wotring, Virginia E.

2014-01-01

Visual Impairment/Intracranial Pressure (VIIP) is a newly recognized risk at NASA. The VIIP project examines the effect of long-term exposure to microgravity on vision of crewmembers before and after they return to Earth. Diamox (acetazolamide) is a medication which is used to decrease intraocular pressure; however, it carries a 3% risk of kidney stones. Astronauts are at a higher risk of kidney stones during spaceflight and the use Diamox would only increase the risk; therefore alternative therapies were investigated. Histamine 2 (H2) antagonist acid blockers such as cimetidine, ranitidine, famotidine and nizatidine are typically used to relieve the symptoms of gastroesophageal reflux disease (GERD). H2 receptors have been found in the human visual system, which has led to research on the use of H2 antagonist blockers to control fluid production in the human eye. Another potential therapeutic strategy is targeted at aquaporins, which are water channels that help maintain fluid homeostasis. Aquaporin antagonists are also known to affect intracranial pressure which can in turn alter intraocular pressure. Studies on aquaporin antagonists suggest high potential for effective treatment. The primary objective of this investigation is to review existing research on alternate medications or therapy to significantly reduce intracranial and intraocular pressure. A literature review was conducted. Even though we do not have all the answers quite yet, a considerable amount of information was discovered, and findings were narrowed, which should allow for more conclusive answers to be found in the near future.

Nonsurgical resolution of gallbladder mucocele in two dogs.

PubMed

Walter, Romanie; Dunn, Marilyn E; d'Anjou, Marc-André; Lécuyer, Manon

2008-06-01

A gallbladder mucocele was diagnosed in 2 dogs. In both dogs, the mucocele resolved with medical treatment but without the need for surgical intervention. A 12-year-old spayed female Miniature Schnauzer had a history of signs of gastrointestinal tract disease and high serum liver enzyme activities. Gallbladder mucocele and hypothyroidism were diagnosed. A 6-year-old neutered mixed-breed dog had chronic intermittent diarrhea and recurrent otitis; gallbladder mucocele and hypothyroidism were diagnosed. The first dog was treated with S-adenosyl-methionine, omega-3 fatty acids, famotidine, ursodiol, and levothyroxine. Substantial improvement in the gastrointestinal tract condition and complete resolution of the gallbladder mucocele within 3 months were evident, but the dog was not available for further follow-up monitoring. The second dog was treated with fenbendazole, ursodiol, and levothyroxine and fed a hypoallergenic diet. One month after evaluation, abdominal ultrasonography revealed that the gallbladder mucocele was resolving, and treatment was continued. Ultrasonographic evaluation 2 and 4 months later revealed complete resolution of the mucocele. Review of the clinical course of 2 dogs in which there was nonsurgical resolution of gallbladder mucocele revealed that surgery is not necessary in all dogs with gallbladder mucocele. Hypothyroidism may have resulted in delayed gallbladder emptying, and its role in the pathogenesis of gallbladder mucocele merits investigation. Despite this information, until further prospective trials with a control group and standardized treatments and follow-up monitoring can be performed, the authors recommend surgical intervention for treatment of dogs with gallbladder mucocele.

Effects of drugs which influence renal transport systems on the urinary excretion of the beta 2-adrenoceptor agonist clenbuterol and the anabolic steroids ethinylestradiol and methyltestosterone.

PubMed

Gleixner, A; Sauerwein, H; Meyer, H H

1997-01-01

The aim of this study was to determine whether the illegal application of clenbuterol, ethinylestradiol and methyltestosterone in cattle as growth promoters can be concealed by co-treatment with drugs that affect urinary excretion. Six male veal calves were fed with 0.8 micrograms clenbuterol kg-1 of body weight (BW), 3.5 micrograms ethinylestradiol kg-1 BW and 35 micrograms methyltestosterone kg-1 BW together twice daily for 28 days. At the eighth day of clenbuterol, ethinylestradiol and methyltestosterone treatment each calf was additionally fed either with probenecid, para-aminohippuric acid, trimethoprim, famotidine or cimetidine at three different doses which were increased in weekly intervals. During the treatment 24 h-urine and blood samples (once daily) were obtained and analysed for clenbuterol, ethinylestradiol and methyltestosterone by specific enzyme immunoassay. By high performance liquid chromatography/enzyme immunoassay it was determined whether these drugs or their metabolites interfered with the immunological detection of the growth promoters. Clenbuterol, ethinylestradiol and methyltestosterone could be detected in plasma and urine throughout the whole experiment. Co-treatment with probenecid led to a five-fold reduction in urinary excretion of ethinylestradiol and co-treatment with trimethoprim led to a three-fold reduction in urinary excretion of clenbuterol. None of the drugs reduced urinary excretion of the growth promoters to concentrations below the limit of detection. The detection of these three growth promoters in urine samples from calves which were co-treated with the drugs tested in this study can thus not be prevented.

Rapid and reliable determination of illegal adulterant in herbal medicines and dietary supplements by LC/MS/MS.

PubMed

Liang, Qionglin; Qu, Jun; Luo, Guoan; Wang, Yiming

2006-02-13

In recent years, dietary supplements and herbal medicines are increasing in popularity all over the world. However, it is problematic that some manufacturers illegally included synthetic drugs in their products. Due to the extremely complex matrices of those products, most existing methods for screening illegal adulterations are time-consuming and liable to false positive. In this paper, a robust LC/MS/MS method for the high-throughput, sensitive and reliable determination of illegal adulterations from herbal medicines and dietary supplements was established. Minimal LC separation was employed and MRM was used to simultaneously monitor the three transitions under their respective optimal collision energy for each compound. Positive results were determined only if well-defined peaks appeared at all of the three transitions and the ratios among the peak areas were within given threshold. In this study, the method had been applied for the screening of nine most commonly adulterated therapeutic substances, such as sildenafil (Viagra) and famotidine, and the lower limits of detection of these compounds ranged from 0.05 to 1.5 ng/ml. Little sample preparation was needed for this method and the analysis time was less than 5 min/sample. The reliability has been demonstrated by the test with blank matrix. Over 200 products that were under suspicion by SDA of China had been assayed and till now no false negative or positive result was found. This method is rapid, simple, reliable and capable of screening multiple adulterants in one run.

Sensitive Indirect Spectrophotometric Method for Determination of H2-Receptor Antagonists in Pharmaceutical Formulations

PubMed Central

Darwish, Ibrahim A.; Hussein, Samiha A.; Mahmoud, Ashraf M.; Hassan, Ahmed I.

2007-01-01

A simple, accurate and sensitive spectrophotometric method has been developed and validated for determination of H2-receptor antagonists: cimetidine, famotidine, nizatidine, and ranitidine hydrochloride. The method was based on the oxidation of these drugs with cerium (IV) in presence of perchloric acid and subsequent measurement of the excess Ce (IV) by its reaction with p-dimethylaminocinnamaldehyde to give a red colored product (λmax at 464 nm). The decrease in the absorption intensity (ΔA) of the colored product, due to the presence of the drug was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under the optimum conditions, linear relationships with good correlation coefficients (0.9985-0.9994) were found between ΔA values and the concentrations of the drugs in a concentration range of 1-16 µg ml-1. The assay limits of detection and quantitation were 0.12-0.44 and 0.37-1.33 µg ml-1, respectively. The method was validated, in terms of accuracy, precision, ruggedness, and robustness; the results were satisfactory. The proposed method was successfully applied to the analysis of the investigated drugs in their pure and pharmaceutical dosage forms (recovery was 98.8-102.5 ± 0.79-1.72%) without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods. PMID:23675034

Formulation and optimisation of raft-forming chewable tablets containing H2 antagonist

PubMed Central

Prajapati, Shailesh T; Mehta, Anant P; Modhia, Ishan P; Patel, Chhagan N

2012-01-01

Purpose: The purpose of this research work was to formulate raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent. Materials and Methods: Tablets were prepared by wet granulation and evaluated for raft strength, acid neutralisation capacity, weight variation, % drug content, thickness, hardness, friability and in vitro drug release. Various raft-forming agents were used in preliminary screening. A 23 full-factorial design was used in the present study for optimisation. The amount of sodium alginate, amount of calcium carbonate and amount sodium bicarbonate were selected as independent variables. Raft strength, acid neutralisation capacity and drug release at 30 min were selected as responses. Results: Tablets containing sodium alginate were having maximum raft strength as compared with other raft-forming agents. Acid neutralisation capacity and in vitro drug release of all factorial batches were found to be satisfactory. The F5 batch was optimised based on maximum raft strength and good acid neutralisation capacity. Drug–excipient compatibility study showed no interaction between the drug and excipients. Stability study of the optimised formulation showed that the tablets were stable at accelerated environmental conditions. Conclusion: It was concluded that raft-forming chewable tablets prepared using an optimum amount of sodium alginate, calcium carbonate and sodium bicarbonate could be an efficient dosage form in the treatment of gastro oesophageal reflux disease. PMID:23580933

Severe ranitidine-induced anaphylaxis: a case report and literature review.

PubMed

Aouam, K; Bouida, W; Ben Fredj, N; Chaabane, A; Boubaker, H; Boukef, R; Boughattas, N A; Nouira, S

2012-08-01

Ranitidine is a generally well-tolerated drug, and serious side effects are rare. However, ranitidine-induced anaphylaxis has been reported on rare occasions. We report on such a case and review other cases reported in the literature. A 36-year-old man with no history of other medications, illnesses or allergic diseases, especially to drugs, consulted our emergency department because of renal colic and epigastric discomfort. He was given 50 mg of ranitidine as a slow intravenous bolus and 20 mg of piroxicam intramuscularly. Within the first minute, the patient developed a cold sweat, trembling, dyspnoea and deterioration of his consciousness. The condition was considered as an anaphylactic shock, and cardiopulmonary resuscitation and inotropic support were immediately commenced. Two days later, he was weaned off the ventilator as he was haemodynamically stable. He was discharged after 7 days. Four weeks later, skin prick tests to ranitidine and piroxicam were performed on the forearm of the patient. He reacted strongly to ranitidine about 10 min later but not to piroxicam. To assess cross-reactivity to other H2- and H1-receptor antagonists in our patient, we subsequently performed prick tests to famotidine, cimetidine and desloratadine and all were negative. We re-emphasize a potentially serious, albeit very rare, adverse effect of ranitidine and summarize other reported cases. This case demonstrates that commonly used, generally safe drugs may on occasions cause serious adverse effects. © 2011 Blackwell Publishing Ltd.

The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria.

PubMed

Laudy, Agnieszka E; Kulińska, Ewa; Tyski, Stefan

2017-01-11

The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs), against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC) value determination in the presence of 1 mM MgSO₄. Furthermore, the influence of non-antibiotics on the susceptibility of clinical strains to quinolones with or without PAβN (Phe-Arg-β-naphthylamide) was investigated. The impacts of PAβN on the susceptibility of bacteria to non-antibiotics suggests that amitriptyline, alendronate, nicergoline, and ticlopidine are substrates of efflux pumps in Gram-negative rods. Amitriptyline/Amitriptylinum showed the highest direct antibacterial activity, with MICs ranging 100-800 mg/L against all studied species. Significant decreases in the MIC values of other active substances (acyclovir, atorvastatin, and famotidine) tested with pump inhibitors were not observed. The investigated non-antibiotic medicinal products did not alter the MICs of quinolones in the absence and in the presence of PAβN to the studied clinical strains of five groups of species.

Advances in gastrointestinal bleeding.

PubMed

Lanas, Ángel

2016-09-01

The main innovations of the latest meeting of the Gastroenterological Association (2016) concerning upper gastrointestinal bleeding from the clinician's perspective can be summarised as follows: a) The Glasgow-Blatchford scale has the best accuracy in predicting the need for surgical intervention and hospital mortality; b) Prognostic scales for non-variceal upper gastrointestinal bleeding are also useful for lower gastrointestinal bleeding; c) Preliminary data suggest that treatment with hemospray does not seem to be superior to current standard treatment in controlling active peptic ulcer bleeding; d) Either famotidine or a proton pump inhibitor may be effective in preventing haemorrhagic recurrence in patients taking aspirin, but this finding needs to be confirmed in further studies; e) There was confirmation of the need to re-introduce antiplatelet therapy as early as possible in patients with antiplatelet-associated gastrointestinal bleeding in order to prevent cardiovascular mortality; f) Routine clinical practice suggests that gastrointestinal or cardiovascular complications with celecoxib or traditional NSAIDs are very low; g) Dabigatran is associated with an increased incidence of gastrointestinal bleeding compared with apixaban or warfarin. At least half of the episodes are located in the lower gastrointestinal tract; h) Implant devices for external ventricular circulatory support are associated with early gastrointestinal bleeding in up to one third of patients; the bleeding is often secondary to arteriovenous malformations. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Inhibiting renin angiotensin system in rate limiting step by aliskiren as a new approach for preventing indomethacin induced gastric ulcers.

PubMed

Halici, Zekai; Polat, Beyzagul; Cadirci, Elif; Topcu, Atilla; Karakus, Emre; Kose, Duygu; Albayrak, Abdulmecit; Bayir, Yasin

2016-10-25

Previously blocking the renin angiotensin system (RAAS) has been effective in the prevention of gastric damage. Therefore, the aim of this study was to investigate the effects of aliskiren, and thus, direct renin blockage, in indomethacin-induced gastric damage model. Effects of aliskiren were evaluated in indomethacin-induced gastric damage model on Albino Wistar rats. Effects of famotidine has been investigated as standard antiulcer agent. Stereological analyses for ulcer area determination, biochemical analyses for oxidative status determination and molecular analyses for tissue cytokine and cyclooxygenase determination were performed on stomach tissues. In addition, to clarify antiulcer effect mechanism of aliskiren pylorus ligation-induced gastric acid secretion model was applied on rats. Aliskiren was able to inhibit indomethacin-induced ulcer formation. It also inhibited renin, and thus, decreased over-produced Angiotensin-II during ulcer formation. Aliskiren improved the oxidative status and cytokine profile of the stomach, which was most probably impaired by increased Angiotensin II concentration. Aliskiren also increased gastroprotective prostaglandin E2 concentration. Finally, aliskiren did not change the gastric acidity in pylorus ligation model. Aliskiren exerted its protective effects on stomach tissue by decreasing inflammatory cytokines and oxidative stress as a result of inhibiting the RAAS, at a rate-limiting step, as well as its end product, angiotensin II. Aliskiren also significantly increased protective factors such as PGE2, but not affect aggressive factors such as gastric acidity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Development of Fluorescence Surrogates to Predict the Photochemical Transformation of Pharmaceuticals in Wastewater Effluents.

PubMed

Yan, Shuwen; Yao, Bo; Lian, Lushi; Lu, Xinchen; Snyder, Shane A; Li, Rui; Song, Weihua

2017-03-07

The photochemical transformation of pharmaceutical and personal care products (PPCPs) in wastewater effluents is an emerging concern for environmental scientists. In the current study, the photodegradation of 29 PPCPs was examined in effluents under simulated solar irradiation. Direct photodegradation, triplet state effluent organic matter ( 3 EfOM*)-mediated and hydroxyl radical (HO • )-mediated degradation are three major pathways in the removal process. With the photodegradation of trace levels of PPCPs, the excitation-emission matrix (EEM) fluorescence intensities of the effluents were also gradually reduced. Therefore, fluorescence peaks have been identified, for the first time, as appropriate surrogates to assess the photodegradation of PPCPs. The humic-like fluorescence peak is linked to direct photolysis-labile PPCPs, such as naproxen, ronidazole, diclofenac, ornidazole, tinidazole, chloramphenicol, flumequine, ciprofloxacin, methadone, and dimetridazole. The tyrosine-like EEM peak is associated with HO • /CO 3 •- -labile PPCPs, such as trimethoprim, ibuprofen, gemfibrozil, atenolol, carbamazepine, and cephalexin. The tryptophan-like peak is associated with 3 EfOM*-labile PPCPs, such as clenbuterol, metoprolol, venlafaxine, bisphenol A, propranolol, ractopamine, salbutamol, roxithromycin, clarithromycin, azithromycin, famotidine, terbutaline, and erythromycin. The reduction in EEM fluorescence correlates well with the removal of PPCPs, allowing a model to be constructed. The solar-driven removal of EEM fluorescence was applied to predict the attenuation of 11 PPCPs in five field samples. A close correlation between the predicted results and the experimental results suggests that fluorescence may be a suitable surrogate for monitoring the solar-driven photodegradation of PPCPs in effluents.

Sofalcone, a mucoprotective agent, increases the cure rate of Helicobacter pylori infection when combined with rabeprazole, amoxicillin and clarithromycin

PubMed Central

Isomoto, Hajime; Furusu, Hisashi; Ohnita, Ken; Wen, Chun-Yang; Inoue, Kenichiro; Kohno, Shigeru

2005-01-01

AIM: The mucoprotective agents, sofalcone and polaprezinc have anti-Helicobacter pylori (H pylori) activities. We determined the therapeutic effects of sofalcone and polaprezinc when combined with rabeprazole, amoxicillin and clarithromycin for Helicobacter pylori infection. METHODS: One hundred and sixty-five consecutive outpatients with peptic ulcer and H pylori infection were randomly assigned to one of the following three groups and medicated for 7 d. Group A: triple therapy with rabeprazole (10 mg twice daily), clarithromycin (200 mg twice daily) and amoxicillin (750 mg twice daily). Group B: sofalcone (100 mg thrice daily) plus the triple therapy. Group C: polaprezinc (150 mg twice daily) plus the triple therapy. Eradication was considered successful if 13C-urea breath test was negative at least 4 wk after cessation of eradication regimens or successive famotidine in the cases of active peptic ulcer. RESULTS: On intention-to-treat basis, H pylori cure was achieved in 43 of 55 (78.2%) patients, 47 of 54 (87.0%) and 45 of 56 (80.4%) for the groups A, B and C respectively. Using per protocol analysis, the eradication rates were 81.1% (43/53), 94.0% (47/50) and 84.9% (45/53) respectively. There was a significant difference in the cure rates between group A and B. Adverse events occurred in 10, 12 and 11 patients, from groups A, B and C respectively, but the events were generally mild. CONCLUSION: The addition of sofalcone, but not polaprezinc, significantly increased the cure rate of H pylori infection when combined with the rabeprazole-amoxicillin-clarithromycin regimen. PMID:15786539

Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice

PubMed Central

Vila-Leahey, Ava; Oldford, Sharon A.; Marignani, Paola A.; Wang, Jun; Haidl, Ian D.; Marshall, Jean S.

2016-01-01

ABSTRACT Histamine receptor 2 (H2) antagonists are widely used clinically for the control of gastrointestinal symptoms, but also impact immune function. They have been reported to reduce tumor growth in established colon and lung cancer models. Histamine has also been reported to modify populations of myeloid-derived suppressor cells (MDSCs). We have examined the impact of the widely used H2 antagonist ranitidine, on both myeloid cell populations and tumor development and spread, in three distinct models of breast cancer that highlight different stages of cancer progression. Oral ranitidine treatment significantly decreased the monocytic MDSC population in the spleen and bone marrow both alone and in the context of an orthotopic breast tumor model. H2 antagonists ranitidine and famotidine, but not H1 or H4 antagonists, significantly inhibited lung metastasis in the 4T1 model. In the E0771 model, ranitidine decreased primary tumor growth while omeprazole treatment had no impact on tumor development. Gemcitabine treatment prevented the tumor growth inhibition associated with ranitidine treatment. In keeping with ranitidine-induced changes in myeloid cell populations in non-tumor-bearing mice, ranitidine also delayed the onset of spontaneous tumor development, and decreased the number of tumors that developed in LKB1−/−/NIC mice. These results indicate that ranitidine alters monocyte populations associated with MDSC activity, and subsequently impacts breast tumor development and outcome. Ranitidine has potential as an adjuvant therapy or preventative agent in breast cancer and provides a novel and safe approach to the long-term reduction of tumor-associated immune suppression. PMID:27622015

Effect of rebamipide on gastric bleeding and ulcerogenic responses induced by aspirin plus clopidogrel under stimulation of acid secretion in rats.

PubMed

Takeuchi, Koji; Takayama, Shinichi; Hashimoto, Erika; Itayama, Misaki; Amagase, Kikuko; Izuhara, Chitose

2014-12-01

We examined the prophylactic effect of rebamipide on gastric bleeding induced by the perfusion of aspirin (acetylsalicylic acid [ASA]) plus clopidogrel under the stimulation of acid secretion in rats. Under urethane anesthesia, acid secretion was stimulated by the i.v. infusion of histamine (8 mg/kg/h), and the stomach was perfused with 25 mmol/L ASA at a rate of 0.4 mL/min. Gastric bleeding was evaluated as the concentration of hemoglobin in the perfusate. Clopidogrel (30 mg/kg) was given p.o. 24 h before the perfusion. Rebamipide (3-30 mg/kg) or other antiulcer drugs were given i.d. before the ASA perfusion. Slight gastric bleeding or damage was observed with the perfusion of ASA under the stimulation of acid secretion, whereas these responses were significantly increased in the presence of clopidogrel. Both omeprazole and famotidine inhibited acid secretion and prevented these responses to ASA plus clopidogrel. Rebamipide had no effect on acid secretion, but dose-dependently prevented gastric bleeding in response to ASA plus clopidogrel, with the degree of inhibition being almost equivalent to that of the antisecretory drugs, and the same effects were obtained with the gastroprotective drugs, irsogladine and teprenone. These agents also reduced the severity of gastric lesions, although the effects were less than those of the antisecretory drugs. These results suggest that the antiplatelet drug, clopidogrel, increases gastric bleeding induced by ASA under the stimulation of acid secretion, and the gastroprotective drug, rebamipide, is effective in preventing the gastric bleeding induced under such conditions, similar to antisecretory drugs. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Adverse effects reported in the use of gastroesophageal reflux disease treatments in children: a 10 years literature review

PubMed Central

Cohen, Shlomi; Bueno de Mesquita, Mirjam; Mimouni, Francis B

2015-01-01

Gastroesophageal reflux (GER) is commonly observed in children, particularly during the first year of life. Pharmacological therapy is mostly reserved for symptomatic infants diagnosed with GER disease (GERD), usually as defined in a recent consensus statement. The purpose of the present article was to review the reported adverse effects of pharmacological agents used in the treatment of paediatric GERD. We conducted this review using the electronic journal database Pubmed and Cochrane database systematic reviews using the latest 10-year period (1 January 2003 to 31 December 2012). Our search strategy included the following keywords: omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole, rantidine, cimetidine, famotidine, nizatidine, domperidone, metoclopramide, betanechol, erythromycin, baclofen, alginate. We used Pubmed’s own filter of: ’child: birth–18 years’. All full articles were reviewed and we only included randomized controlled trials retrieved from our search. We addressed a summary of our search on a drug-by-drug basis with regard to its mechanism of action and clinical applications, and reviewed all of the adverse effects reported and the safety profile of each drug. Adverse effects have been reported in at least 23% of patients treated with histamine H2 receptor antagonists (H2RAs) and 34% of those treated with proton pump inhibitors (PPIs), and mostly include headaches, diarrhoea, nausea (H2RAs and PPIs) and constipation (PPIs). Acid suppression may place immune-deficient infants and children, or those with indwelling catheters, at risk for the development of lower respiratory tract infections and nosocomial sepsis. Prokinetic agents have many adverse effects, without major benefits to support their routine use. PMID:25752807

Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity

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

Cosgrove, Benjamin D.; Cell Decision Processes Center, Massachusetts Institute of Technology, Cambridge, MA; Biotechnology Process Engineering Center, Massachusetts Institute of Technology, Cambridge, MA

Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF,more » IFN{gamma}, IL-1{alpha}, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1{alpha}, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.« less

Development of a multi-residue analytical methodology based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for screening and trace level determination of pharmaceuticals in surface and wastewaters.

PubMed

Gros, Meritxell; Petrović, Mira; Barceló, Damiá

2006-11-15

This paper describes development, optimization and validation of a method for the simultaneous determination of 29 multi-class pharmaceuticals using off line solid phase extraction (SPE) followed by liquid chromatography-triple quadrupole mass spectrometry (LC-MS-MS). Target compounds include analgesics and non-steroidal anti-inflammatories (NSAIDs), lipid regulators, psychiatric drugs, anti-histaminics, anti-ulcer agent, antibiotics and beta-blockers. Recoveries obtained were generally higher than 60% for both surface and wastewaters, with exception of several compounds that yielded lower, but still acceptable recoveries: ranitidine (50%), sotalol (50%), famotidine (50%) and mevastatin (34%). The overall variability of the method was below 15%, for all compounds and all tested matrices. Method detection limits (MDL) varied between 1 and 30ng/L and from 3 to 160ng/L for surface and wastewaters, respectively. The precision of the method, calculated as relative standard deviation (R.S.D.), ranged from 0.2 to 6% and from 1 to 11% for inter and intra-day analysis, respectively. A detailed study of matrix effects was performed in order to evaluate the suitability of different calibration approaches (matrix-matched external calibration, internal calibration, extract dilution) to reduce analyte suppression or enhancement during instrumental analysis. The main advantages and drawbacks of each approach are demonstrated, justifying the selection of internal standard calibration as the most suitable approach for our study. The developed analytical method was successfully applied to the analysis of pharmaceutical residues in WWTP influents and effluents, as well as in river water. For both, river and wastewaters, the most ubiquitous compounds belonged to the group of anti-inflammatories and analgesics, antibiotics, the lipid regulators being acetaminophen, trimethoprim, ibuprofen, ketoprofen, atenolol, propranolol, mevastatin, carbamazepine and ranitidine the most frequently

Novel and emerging treatments for autism spectrum disorders: a systematic review.

PubMed

Rossignol, Daniel A

2009-01-01

Currently, only one medication (risperidone) is FDA-approved for the treatment of autism spectrum disorders (ASD). Perhaps for this reason, the use of novel, unconventional, and off-label treatments for ASD is common, with up to 74% of children with ASD using these treatments; however, treating physicians are often unaware of this usage. A systematic literature search of electronic scientific databases was performed to identify studies of novel and emerging treatments for ASD, including nutritional supplements, diets, medications, and nonbiological treatments. A grade of recommendation ("Grade") was then assigned to each treatment using a validated evidence-based guideline as outlined in this review: A: Supported by at least 2 prospective randomized controlled trials (RCTs) or 1 systematic review. B: Supported by at least 1 prospective RCT or 2 nonrandomized controlled trials. C: Supported by at least 1 nonrandomized controlled trial or 2 case series. D: Troublingly inconsistent or inconclusive studies or studies reporting no improvements. Potential adverse effects for each treatment were also reviewed. Grade A treatments for ASD include melatonin, acetylcholinesterase inhibitors, naltrexone, and music therapy. Grade B treatments include carnitine, tetrahydrobiopterin, vitamin C, alpha-2 adrenergic agonists, hyperbaric oxygen treatment, immunomodulation and anti-inflammatory treatments, oxytocin, and vision therapy. Grade C treatments for ASD include carnosine, multivitamin/mineral complex, piracetam, polyunsaturated fatty acids, vitamin B6/magnesium, elimination diets, chelation, cyproheptadine, famotidine, glutamate antagonists, acupuncture, auditory integration training, massage, and neurofeedback. The reviewed treatments for ASD are commonly used, and some are supported by prospective RCTs. Promising treatments include melatonin, antioxidants, acetylcholinesterase inhibitors, naltrexone, and music therapy. All of the reviewed treatments are currently considered

Does common prescription medication affect the rate of orthodontic tooth movement? A systematic review.

PubMed

Makrygiannakis, Militiadis A; Kaklamanos, Eleftherios G; Athanasiou, Athanasios E

2018-03-06

As the taking of any medication may theoretically affect the complex pathways responsible for periodontal tissue homeostasis and the events leading to orthodontic tooth movement, it is considered important for the orthodontist to be able to identify prospective patients' history and patterns of pharmaceutical consumption. To systematically investigate and appraise the quality of the available evidence regarding the effect of commonly prescribed medications on the rate of orthodontic tooth movement. Search without restrictions in eight databases and hand searching until June 2017. Controlled studies investigating the effect of commonly prescribed medications with emphasis on the rate of orthodontic tooth movement. Following study retrieval and selection, relevant data was extracted and the risk of bias was assessed using the SYRCLE's Risk of Bias Tool. Twenty-seven animal studies, involving various pharmacologic and orthodontic interventions, were finally identified. Most studies were assessed to be at unclear or high risk of bias. The rate of orthodontic tooth movement was shown to increase after the administration of diazepam, Vitamin C and pantoprazole, while simvastatin, atorvastatin, calcium compounds, strontium ranelate, propranolol, losartan, famotidine, cetirizine, and metformin decreased the rate of orthodontic tooth movement. No interference with the rate of orthodontic tooth movement was reported for phenytoin, phenobarbital and zinc compounds, whereas, inconsistent or conflicting effects were noted after the administration of L-thyroxine, lithium compounds, fluoxetine and insulin. The quality of the available evidence was considered at best as low. Commonly prescribed medications may exhibit variable effects on the rate of orthodontic tooth movement. Although the quality of evidence was considered at best as low, raising reservations about the strength of the relevant recommendations, the clinician should be capable of identifying patients taking

Antiulcer and in vitro antioxidant activities of Jasminum grandiflorum L.

PubMed

Umamaheswari, M; Asokkumar, K; Rathidevi, R; Sivashanmugam, A T; Subhadradevi, V; Ravi, T K

2007-04-04

The study was aimed at evaluating the antiulcer and antioxidant activities of 70% ethanolic axtract of leaves of Jasminum grandiflorum L. (JGLE). The leaves of Jasminum grandiflorum L. (Family: Oleaceae) is used in folk medicine for treating ulcerative stomatitis, skin diseases, ulcers, wounds, corns - a hard or soft hyperkeratosis of the sole of the human foot secondary to friction and pressure (Stedman's Medical Dictionary, 28th ed. Lippincott Williams & Wilkins, Philadelphia. p. 443), etc., Antiulcerogenic activity of JGLE (100 and 200 mg/kg, b.w., orally) was evaluated employing aspirin + pylorus ligation (APL) and alcohol (AL) induced acute gastric ulcer models and ulcer-healing activity using acetic acid-induced (AC) chronic ulcer model in rats. Both the antisecretory and cytoprotection hypothesis were evaluated. The antioxidant activity of JGLE has been assayed by using in vitro methods like 2,2-diphenyl-1-picrylhydrazylhydrate (DPPH) assay, reductive ability, superoxide anion scavenging activity, nitric oxide scavenging activity and total phenolic content, in order to explain the role of antioxidant principles in the antiulcerogenic activity of the extract. There was a significant (P<0.01) dose-dependent decrease in the ulcerative lesion index produced by all the three models in rats as compared to the standard drug famotidine (20 mg/kg, b.w. orally). The reduction in gastric fluid volume, total acidity and an increase in the pH of the gastric fluid in APL rats proved the antisecretory activity of JGLE. Additionally, JGLE completely healed the ulcer within 20 days of treatment in AC model as evidenced by histopathological studies. Like antiulcer activity, the free radical scavenging activities of JGLE depends on concentration and increased with increasing amount of the extract. These results suggest that leaves of Jasminum grandiflorum possess potential antiulcer activity, which may be attributed to its antioxidant mechanism of action.

In Vitro Dissolution of Fluconazole and Dipyridamole in Gastrointestinal Simulator (GIS), Predicting in Vivo Dissolution and Drug-Drug Interaction Caused by Acid-Reducing Agents.

PubMed

Matsui, Kazuki; Tsume, Yasuhiro; Amidon, Gregory E; Amidon, Gordon L

2015-07-06

Weakly basic drugs typically exhibit pH-dependent solubility in the physiological pH range, displaying supersaturation or precipitation along the gastrointestinal tract. Additionally, their oral bioavailabilities may be affected by coadministration of acid-reducing agents that elevate gastric pH. The purpose of this study was to assess the feasibility of a multicompartmental in vitro dissolution apparatus, Gastrointestinal Simulator (GIS), in predicting in vivo dissolution of certain oral medications. In vitro dissolution studies of fluconazole, a BCS class I, and dipyridamole, a BCS class II weak bases (class IIb), were performed in the GIS as well as United States Pharmacopeia (USP) apparatus II and compared with the results of clinical drug-drug interaction (DDI) studies. In both USP apparatus II and GIS, fluconazole completely dissolved within 60 min regardless of pH, reflecting no DDI between fluconazole and acid-reducing agents in a clinical study. On the other hand, seven-fold and 15-fold higher concentrations of dipyridamole than saturation solubility were observed in the intestinal compartments in GIS with gastric pH 2.0. Precipitation of dipyridamole was also observed in the GIS, and the percentage of dipyridamole in solution was 45.2 ± 7.0%. In GIS with gastric pH 6.0, mimicking the coadministration of acid-reducing agents, the concentration of dipyridamole was equal to its saturation solubility, and the percentage of drug in solution was 9.3 ± 2.7%. These results are consistent with the clinical DDI study of dipyridamole with famotidine, which significantly reduced the Cmax and area under the curve. An In situ mouse infusion study combined with GIS revealed that high concentration of dipyridamole in the GIS enhanced oral drug absorption, which confirmed the supersaturation of dipyridamole. In conclusion, GIS was shown to be a useful apparatus to predict in vivo dissolution for BCS class IIb drugs.

Monitoring simultaneous photocatalytic-ozonation of mixture of pharmaceuticals in the presence of immobilized TiO2 nanoparticles using MCR-ALS: Identification of intermediates and multi-response optimization approach

NASA Astrophysics Data System (ADS)

Fathinia, Mehrangiz; Khataee, Alireza; Naseri, Abdolhosein; Aber, Soheil

2015-02-01

The present study has focused on the degradation of a mixture of three pharmaceuticals, i.e. methyldopa (MDP), nalidixic acid (NAD) and famotidine (FAM) which were quantified simultaneously during photocatalytic-ozonation process. The experiments were conducted in a semi-batch reactor where TiO2 nanoparticles (crystallites mean size 8 nm) were immobilized on ceramic plates irradiated by UV-A light in the proximity of oxygen and/or ozone. The surface morphology and roughness of the bare and TiO2-coated ceramic plates were analyzed using scanning electron microscopy (SEM) and atomic force microscopy (AFM). An analytical methodology was successfully developed based on both recording ultraviolet-visible (UV-Vis) spectra during the degradation process and a data analysis using multivariate curve resolution with alternating least squares (MCR-ALS). This methodology enabled the researchers to obtain the concentration and spectral profiles of the chemical compounds which were involved in the process. A central composite design was used to study the effect of several factors on multiple responses namely MDP removal (Y1), NAD removal (Y2) and FAM removal (Y3) in the simultaneous photocatalytic-ozonation of these pharmaceuticals. A multi-response optimization procedure based on global desirability of the factors was used to simultaneously maximize Y1, Y2 and Y3. The results of the global desirability revealed that 8 mg/L MAD, 8 mg/L NAD, 8 mg/L FAM, 6 L/h ozone flow rate and a 30 min-reaction time were the best conditions under which the optimized values of various responses were Y1 = 95.03%, Y2 = 84.93% and Y3 = 99.15%. Also, the intermediate products of pharmaceuticals generated in the photocatalytic-ozonation process were identified by gas chromatography coupled to mass spectrometry.

Clinical experience with pantoprazole in gastroesophageal reflux disease.

PubMed

Avner, D L

2000-10-01

Pantoprazole is a new proton pump inhibitor indicated for the treatment of erosive esophagitis associated with gastroesophageal reflux disease (GERD) and is available in both oral and intravenous (IV) formulations. This paper reviews the pharmacologic properties of pantoprazole and summarizes the findings from clinical studies of this drug. This review was compiled from the published literature, abstracts from clinical trials, and data on file with the manufacturer of pantoprazole. Pantoprazole selectively accumulates in the acidic environment of gastric parietal cells and acts at the final step of acid secretion by binding 2 key cysteine residues of the proton pump involved in gastric acid production. The bioavailability of pantoprazole is not altered by concomitant administration of food or antacids or with repeated dosing. Both oral and IV formulations of pantoprazole exhibit linear pharmacokinetics. Several clinical trials have proved pantoprazole superior to histamine-2-receptor antagonists (H2RAs) in reducing acid secretion and elevating gastric pH levels. Pantoprazole has been shown to be more effective than ranitidine (P < 0.05), famotidine (P < 0.001), and nizatidine (P < 0.05), and at least as effective as omeprazole, in healing erosive esophagitis and relieving associated symptoms of GERD, including regurgitation. Pantoprazole is also more effective than the H2RA nizatidine for the treatment of nighttime heartburn (P < 0.05). Studies have shown pantoprazole to be well tolerated; adverse events, including headache, diarrhea, flatulence, abdominal pain, eructation, nausea, and rash, occurred in < or = 6% of patients. The oral and IV formulations of pantoprazole are equally potent in inhibiting gastric acid secretion; thus, switching between formulations requires no dosage adjustments. Special patient populations, including the elderly and patients with renal or mild to moderate hepatic impairment, can take pantoprazole without an adjustment in dosage

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats.

PubMed

Xue, Xiao-Chang; Wu, Yong-Jie; Gao, Ming-Tang; Li, Wen-Guang; Zhao, Ning; Wang, Zeng-Lu; Bao, Chun-Jie; Yan, Zhen; Zhang, Ying-Qi

2004-04-01

To investigate the protective effects of gastric pentadecapeptide BPC 157 on acute and chronic gastric ulcers in rats and to compare the results in therapy of human gastric ulcers by different administration methods. Gastric pentadecapeptide BPC 157 was administered (initial single or continuous administration) into rats either intragastrically or intramuscularly before (induced acute gastric ulcer) or after (induced chronic gastric ulcer) the applications of inducing agents, and each animal was sacrificed to observe the protective effects of BPC 157 on gastric ulcers. Both intramuscular (im) and intragastric (ig) administration of BPC 157 could apparently reduce the ulcer area and accelerate the healing of induced ulcer in different models and the effect of im administered BPC 157 was better than that of ig. The rats treated with higher dosages (400 ng/kg, 800 ng/kg) of BPC 157 (im and ig) showed significantly less lesion (P<0.01 vs excipient or saline control), the inhibition ratio of ulcer formation varied between 45.7% and 65.6%, from all measurements except 400 ng/kg BPC 157 in pylorus ligation induced model (P<0.05), in which the inhibition rate was 54.2%. When im administered (800 ng/kg BPC 157) in three models, the inhibition ratio of ulcer formation was 65.5%, 65.6% and 59.9%, respectively, which was better than that of famotidine (its inhibition rate was 60.8%, 57.2% and 34.3%, respectively). Continuous application of BPC 157 (in chronic acetate induced gastric ulcer) could accelerate rebuilding of glandular epithelium and formation of granulation tissue (P<0.05 at 200 ng/kg and P<0.01 at 400 ng/kg and 800 ng/kg vs excipient or saline control). Both im and ig administered gastric pentadecapeptide BPC 157 can apparently ameliorate acute gastric ulcer in rats and antagonize the protracted effect of acetate challenge on chronic ulcer. The effect of im administration of BPC 157 is better than that of ig, and the effective dosage of the former is lower than

Protective effects of pentadecapeptide BPC 157 on gastric ulcer in rats

PubMed Central

Xue, Xiao-Chang; Wu, Yong-Jie; Gao, Ming-Tang; Li, Wen-Guang; Zhao, Ning; Wang, Zeng-Lu; Bao, Chun-Jie; Yan, Zhen; Zhang, Ying-Qi

2004-01-01

AIM: To investigate the protective effects of gastric pentadecapeptide BPC 157 on acute and chronic gastric ulcers in rats and to compare the results in therapy of human gastric ulcers by different administration methods. METHODS: Gastric pentadecapeptide BPC 157 was administered (initial single or continuous administration) into rats either intragastrically or intramuscularly before (induced acute gastric ulcer) or after (induced chronic gastric ulcer) the applications of inducing agents, and each animal was sacrificed to observe the protective effects of BPC 157 on gastric ulcers. RESULTS: Both intramuscular (im) and intragastric (ig) administration of BPC 157 could apparently reduce the ulcer area and accelerate the healing of induced ulcer in different models and the effect of im administered BPC 157 was better than that of ig. The rats treated with higher dosages (400 ng/kg, 800 ng/kg) of BPC 157 (im and ig) showed significantly less lesion (P < 0.01 vs excipient or saline control), the inhibition ratio of ulcer formation varied between 45.7% and 65.6%, from all measurements except 400 ng/kg BPC 157 in pylorus ligation induced model (P < 0.05), in which the inhibition rate was 54.2%. When im administered (800 ng/kg BPC 157) in three models, the inhibition ratio of ulcer formation was 65.5%, 65.6% and 59.9%, respectively, which was better than that of famotidine (its inhibition rate was 60.8%, 57.2% and 34.3%, respectively). Continuous application of BPC 157 (in chronic acetate induced gastric ulcer) could accelerate rebuilding of glandular epithelium and formation of granulation tissue (P < 0.05 at 200 ng/kg and P < 0.01 at 400 ng/kg and 800 ng/kg vs excipient or saline control). CONCLUSION: Both im and ig administered gastric pentadecapeptide BPC 157 can apparently ameliorate acute gastric ulcer in rats and antagonize the protracted effect of acetate challenge on chronic ulcer. The effect of im administration of BPC 157 is better than that of ig, and the

Impact of the Minimum Pricing Policy and introduction of brand (generic) substitution into the Pharmaceutical Benefits Scheme in Australia.

PubMed

McManus, P; Birkett, D J; Dudley, J; Stevens, A

2001-01-01

To describe the effects of introducing the Minimum Pricing Policy (MPP) and generic (brand) substitution in 1990 and 1994 respectively on the dispensing of Pharmaceutical Benefits Scheme (PBS) prescriptions both at the aggregate and individual patient level. The relative proportion of prescriptions with a brand premium and those at benchmark was examined 4 years after introduction of the MPP and again 5 years later after generic substitution by pharmacists was permitted. To determine the impact of a price signal at the individual level, case studies involving a patient tracking methodology were conducted on two drugs (fluoxetine and ranitidine) that received a brand premium. From a zero base when the MPP was introduced in 1990, there were 5.4 million prescriptions (17%) dispensed for benchmark products 4 years later in 1994. At this stage generic (brand) substitution by pharmacists was then permitted and the market share of benchmark brands increased to 45% (25.2 million) by 1999. In the patient tracking studies, a significantly lower proportion of patients was still taking the premium brand of fluoxetine 3 months after the introduction of a price signal compared with patients taking paroxetine which did not have a generic competitor. This was also the case for the premium brand of ranitidine when compared to famotidine. The size of the price signal also had a marked effect on dispensing behaviour with the drug with the larger premium (fluoxetine) showing a significantly greater switch away from the premium brand to the benchmark product. The introduction in 1990 of the Minimum Pricing Policy without allowing generic substitution had a relatively small impact on the selection of medicines within the Pharmaceutical Benefits Scheme. However the effect of generic substitution at the pharmacist level, which was introduced in December 1994, resulted in a marked increase in the percentage of eligible PBS items dispensed at benchmark. Case studies showed a larger premium

Fate and distribution of pharmaceuticals in wastewater and sewage sludge of the conventional activated sludge (CAS) and advanced membrane bioreactor (MBR) treatment.

PubMed

Radjenović, Jelena; Petrović, Mira; Barceló, Damià

2009-02-01

In this paper we report on the performances of full-scale conventional activated sludge (CAS) treatment and two pilot-scale membrane bioreactors (MBRs) in eliminating various pharmaceutically active compounds (PhACs) belonging to different therapeutic groups and with diverse physico-chemical properties. Both aqueous and solid phases were analysed for the presence of 31 pharmaceuticals included in the analytical method. The most ubiquitous contaminants in the sewage water were analgesics and anti-inflammatory drugs ibuprofen (14.6-31.3 microg/L) and acetaminophen (7.1-11.4 microg/L), antibiotic ofloxacin (0.89-31.7 microg/L), lipid regulators gemfibrozil (2.0-5.9 microg/L) and bezafibrate (1.9-29.8 microg/L), beta-blocker atenolol (0.84-2.8 microg/L), hypoglycaemic agent glibenclamide (0.12-15.9 microg/L) and a diuretic hydrochlorothiazide (2.3-4.8 microg/L). Also, several pharmaceuticals such as ibuprofen, ketoprofen, diclofenac, ofloxacin and azithromycin were detected in sewage sludge at concentrations up to 741.1, 336.3, 380.7, 454.7 and 299.6 ng/g dry weight. Two pilot-scale MBRs exhibited enhanced elimination of several pharmaceutical residues poorly removed by the CAS treatment (e.g., mefenamic acid, indomethacin, diclofenac, propyphenazone, pravastatin, gemfibrozil), whereas in some cases more stable operation of one of the MBR reactors at prolonged SRT proved to be detrimental for the elimination of some compounds (e.g., beta-blockers, ranitidine, famotidine, erythromycin). Moreover, the anti-epileptic drug carbamazepine and diuretic hydrochlorothiazide by-passed all three treatments investigated. Furthermore, sorption to sewage sludge in the MBRs as well as in the entire treatment line of a full-scale WWTP is discussed for the encountered analytes. Among the pharmaceuticals encountered in sewage sludge, sorption to sludge could be a relevant removal pathway only for several compounds (i.e., mefenamic acid, propranolol, and loratidine). Especially in the

Impact of food and the proton pump inhibitor rabeprazole on the pharmacokinetics of GDC-0941 in healthy volunteers: bench to bedside investigation of pH-dependent solubility.

PubMed

Ware, Joseph A; Dalziel, Gena; Jin, Jin Y; Pellett, Jackson D; Smelick, Gillian S; West, David A; Salphati, Laurent; Ding, Xiao; Sutton, Rebecca; Fridyland, Jane; Dresser, Mark J; Morrisson, Glenn; Holden, Scott N

2013-11-04

GDC-0941 is an orally administered potent, selective pan-inhibitor of phosphatidylinositol 3-kinases (PI3Ks) with good preclinical antitumor activity in xenograft models and favorable pharmacokinetics and tolerability in phase 1 trials, and it is currently being investigated in phase II clinical trials as an anti-cancer agent. In vitro solubility and dissolution studies suggested that GDC-0941, a weak base, displays significant pH-dependent solubility. Moreover, preclinical studies conducted in famotidine-induced hypochlorhydric dog suggested that the pharmacokinetics of GDC-0941 may be sensitive to pharmacologically induced hypochlorhydria. To investigate the clinical significance of food and pH-dependent solubility on GDC-0941 pharmacokinetics a four-period, two-sequence, open-label, randomized, crossover study was conducted in healthy volunteers. During the fasting state, GDC-0941 was rapidly absorbed with a median Tmax of 2 h. The presence of a high-fat meal delayed the absorption of GDC-0941, with a median Tmax of 4 h and a modest increase in AUC relative to the fasted state, with an estimated geometric mean ratio (GMR, 90% CI) of fed/fasted of 1.28 (1.08, 1.51) for AUC0-∞ and 0.87 (0.70, 1.06) for Cmax. The effect of rabeprazole (model PPI) coadministration on the pharmacokinetics of GDC-0941 was evaluated in the fasted and fed state. When comparing the effect of rabeprazole + GDC-0941 (fasted) to baseline GDC-0941 absorption in a fasted state, GDC-0941 median Tmax was unchanged, however, both Cmax and AUC0-∞ decreased significantly after pretreatment with rabeprazole, with an estimated GMR (90% CI) of 0.31 (0.21, 0.46) and 0.46 (0.35, 0.61), respectively for both parameters. When rabeprazole was administered in the presence of the high-fat meal, the impact of food did not fully reverse the pH effect; the overall effect of rabeprazole on AUC0-∞ was somewhat attenuated by the high-fat meal (estimate GMR of 0.57, with 90% CI, 0.50, 0.65) but unchanged for