omeprazole, Prilosec
[Differences in the release of omeprazole in 4 commercial preparations: influence of pH and ionic concentration]

[Article in Spanish]

Navarro MA, Raei N, Torres F, Granero L, Garcia-Zaragoza E, Esplugues JV, Esteban Peris J.

Departamento de Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad de Valencia.

The influence of exposition to different ionic concentrations and pH values on the subsequent in vitro dissolution of omeprazole at pH 6.8 was studied in four enteric-coated commercial formulations. Assays were done using an experimental protocol similar to that recommended in Delayed-Release (Enteric Coated) Articles-General Drug Release Standards (USP 23) slightly modified to achieve similar pH values to commonly observed in patients under omeprazole treatment. Omeprazole capsules were exposed during 1 or 2 hours to four different pH values: 4.8, 5.0, 5.2, and 5.4 and two NaCl concentrations: 75 and 225 mM. After that, dissolution tests at pH 6.8 were performed. Three formulations (Emeproton, Pepticum and Ulceral) released different percents of the encapsulated dose at the above acidic mediums and, consequently, the omeprazole dissolved underwent a remarkable degradation. The drug contained in the enteric-coated granules of Losec was not released and therefore the amount of omeprazole dissolved at pH 6.8 from Losec capsules was higher than the obtained with the other three preparations tested.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9549180&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
[Seven-day omeprazole, clarithromycin, and amoxicillin for the therapy of Helicobacter pylori infection]

[Article in Spanish]

Comet R, Calvet X, Navarro M, Garcia N, Sanfeliu I.

Servicio de Medicina Intern Consorci Hospitalari del Parc Tauli, Sabadell, Barcelona.

BACKGROUND: There are few series reporting efficacy of seven-day therapy with omeprazole, amoxicillin and clarithromycin for cure of Helicobacter pylori infection in Spain. The aim of the present study was to evaluate the efficacy of this treatment to eradicate H. pylori infection. PATIENTS AND METHODS: One hundred consecutive patients with peptic ulcer disease and H. pylori infection were evaluated for eradication therapy between January and November 1996. Four of them were excluded because of reported penicillin allergy. The remaining 96 patients received a seven days course of omeprazole 20 mg/12h, clarithromycin 500 mg/12h and amoxicillin 1 g/12h. The efficacy of the treatment was evaluated at 2-4 months after therapy either by endoscopic biopsy or by 13C urea breath-test. RESULTS: Seventy-eight patients were found to be cured at the control evaluation. Intention to treat analysis showed a cure rate of 81.3% (95% CI: 74-89%). Per protocol analysis showed a cure rate of 85.7% (95% CI: 79-93%)--78 out of 91 patient who returned for follow-up-. Compliance with the treatment was good in 94.5% of patients. Five patients presented mild side effects (diarrhea, abdominal pain, oral candidiasis and metallic taste). None of them had to interrupt the treatment. CONCLUSION: Seven-day therapy with omeprazole, amoxicillin and clarithromycin achieves a 85% cure rate of H. pylori infection in our area.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9549183&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Protective effects of sucralfate and omeprazole on gastric mucosal damage induced by ethanol in rats.

Kaya N, Boyunapa H, Baris S, Kahraman H, Altintop L.

Section of Gastroenterology, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey.

Studies on the protective effect of omeprazole, a proton-pump inhibitor, against damage to the rat gastric mucosa induced by strong irritants, are few and contradictory. We have investigated the protective effects of omeprazole and sucralfate against gastric mucosal damage induced by ethanol in rats. The study was performed on 4 groups of 10 rats each. Group A received omeprazole 7 mg/kg/day intraperitoneally (i.p.) for 7 days. Group B received an equivalent volume of 0.9% sodium chloride i.p. for 7 days, while no drugs were given to groups C and D. After 1 week, following 24 hours of fasting, group A received omeprazole 7 mg/kg, group B received an equivalent volume of 0.9% sodium chloride group C received omeprazole 7 mg/kg i.p. and group D received sucralfate, 100 mg/kg intragastrically (i.g.). 4 hours after groups A, B and C received the last medication and 30 minutes after group D received sucralfate, ethanol 95% was given i.g. All rats were sacrificed 1 hour after ethanol application and their stomachs were removed for macroscopic and microscopic examination. It was found that sucralfate was effective in preventing gastric lesions induced by ethanol. There was a significant difference between the sucralfate group and the other group (p < 0.001). Omeprazole was ineffective in preventing gastric lesions, either given as a single dose or after administration for 7 days. Our results indicate that sucralfate has a protective effect on gastric lesions induced by ethanol and omeprazole applied i.p. has no protective effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9553204&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations.

Lasker JM, Wester MR, Aramsombatdee E, Raucy JL.

Department of Biochemistry, Mount Sinai School of Medicine, New York, New York 10029, USA.

Individuals with drug metabolism polymorphisms involving CYP2C enzymes exhibit deficient oxidation of important therapeutic agents, including S-mephenytoin, omeprazole, warfarin, tolbutamide, and nonsteroidal anti-inflammatory drugs. While recombinant CYP2C19 and CYP2C9 proteins expressed in yeast or Escherichia coli have been shown to oxidize these agents, the capacity of the corresponding native P450s isolated from human liver to do so is ill defined. To that end, we purified CYP2C19, CYP2C9, and CYP2C8 from human liver samples using conventional chromatographic techniques and examined their capacity to oxidize S-mephenytoin, omeprazole, and tolbutamide. Upon reconstitution, CYP2C19 metabolized S-mephenytoin and omeprazole at rates that were 11- and 8-fold higher, respectively, than those of intact liver microsomes, whereas neither CYP2C9 nor CYP2C8 displayed appreciable metabolic activity with these substrates. CYP2C19 also proved an efficient catalyst of tolbutamide metabolism, exhibiting a turnover rate similar to CYP2C9 preparations (2.0-6.4 vs 2.4-4.3 nmol hydroxytolbutamide formed/min/nmol P450). The kinetic parameters of CYP2C19-mediated tolbutamide hydroxylation (Km = 650 microM, Vmax = 3.71 min-1) somewhat resembled those of the CYP2C9-catalyzed reaction (Km = 178-407 microM, Vmax = 2.95-7.08 min-1). Polyclonal CYP2C19 antibodies markedly decreased S-mephenytoin 4'-hydroxylation (98% inhibition) and omeprazole 5-hydroxylation (85% inhibition) by human liver microsomes. CYP2C19 antibodies also potently inhibited (>90%) microsomal tolbutamide hydroxylation, which was similar to the inhibition (>85%) observed with antibodies to CYP2C9. Moreover, excellent correlations were found between immunoreactive CYP2C19 content, S-mephenytoin 4'-hydroxylase activity (r = 0.912; P < 0. 001), and omeprazole 5-hydroxylase activity (r = 0.906; P < 0.001) in liver samples from 13-17 different subjects. A significant relationship was likewise observed between microsomal tolbutamide hydroxylation and CYP2C9 content (r = 0.664; P < 0.02) but not with CYP2C19 content (r = 0.393; P = 0.184). Finally, immunoquantitation revealed that in these human liver samples, expression of CYP2C9 (88. 5 +/- 36 nmol/mg) was 5-fold higher than that of CYP2C19 (17.8 +/- 14 nmol/mg) and nearly 8-fold higher than that of CYP2C8 (11.5 +/- 12 nmol/mg). Our results, like those obtained with recombinant CYP2C enzymes, indicate that CYP2C19 is a primary determinant of S-mephenytoin 4'-hydroxylation and low-Km omeprazole 5-hydroxylation in human liver. Despite its tolbutamide hydroxylase activity, the low levels of hepatic CYP2C19 expression (relative to CYP2C9) may preclude an important role for this enzyme in hepatic tolbutamide metabolism and any polymorphisms thereof. Copyright 1998 Academic Press.

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omeprazole, Prilosec
Molecular modelling and quantitative structure-activity relationship studies on the interaction of omeprazole with cytochrome P450 isozymes.

Lewis DF, Lake BG.

Molecular Toxicology Group, Centre for Toxicology, School of Biological Sciences, University of Surrey, Guildford, UK.

Molecular modelling of the anti-ulcerative agent, omeprazole, with the putative active sites of cytochromes P4503A4 and P4502C19, enzymes which are the major catalysts of omeprazole metabolism in man, are reported. Interactive docking of omeprazole in both CYP3A4 and CYP2C19 gives rise to binding orientations which are consistent with both the known sites of metabolism reported for these isoforms and with evidence from site-directed mutagenesis experiments on CYP2C19, a P450 associated with genetic polymorphism in human drug metabolism. The potential P450 enzymic interactions, inhibition and induction of omeprazole are discussed in the light of molecular modelling and QSAR (quantitative structure-activity relationship) studies on related compounds.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9585098&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Genetic polymorphism of the hepatic cytochrome P450 2C19 in north Indian subjects.

Lamba JK, Dhiman RK, Kohli KK.

Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

One hundred unrelated healthy North Indian subjects were phenotyped with respect to their ability to metabolize omeprazole to 5-hydroxyomeprazole. Each volunteer was requested to ingest 20 mg (57.9 mumol) omeprazole. Urine was collected for a period of 8 hours and the amount of 5-hydroxyomeprazole excreted was estimated by HPLC. Histogram, probit, and normal test variable plots showed the antimode value for the log hydroxylation index of omeprazole to be 1.7. Of 100 North Indian subjects, 11 demonstrated log hydroxylation index values more than 1.7. Thus it is inferred that the frequency of occurrence of poor metabolizers of omeprazole in North Indian subjects is 11% (95% confidence interval, 5% to 17%). From the Hardy-Weinberg Law it was computed that the frequency of occurrence of the mutant allele of hepatic CYP2C19 in the North Indian subjects was 0.33.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9585796&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Increased hepatocyte growth factor content in rat stomach during omeprazole treatment.

Kinoshita Y, Hassan MS, Kawamura M, Matsushima Y, Okada A, Maekawa T, Fukui H, Waki S, Kishi K, Chiba T.

Department of Medicine, Kobe University School of Medicine, Japan.

BACKGROUND AND AIMS: Hepatocyte growth factor (HGF) is a potent mitogen of gastric epithelial cells, and its production is stimulated during the healing of gastric mucosal lesions. In this study, the effect of a proton pump inhibitor, omeprazole, on the production and degradation of HGF in the stomach was examined to elucidate the mechanism of the omeprazole-induced acceleration of gastric mucosal healing. METHODS: Indomethacin-induced gastric mucosal lesions were induced in rats with or without omeprazole pretreatment. HGF gene expression and the content of HGF was investigated in the rat stomach. HGF degradation by gastric juice was also tested. RESULTS: In omeprazole-treated rats, the healing of gastric mucosal lesions was accelerated in comparison with those of untreated rats. Although omeprazole treatment did not enhance the indomethacin-induced increase in HGF gene expression, it significantly augmented the gastric HGF content. Furthermore, omeprazole increased the gastric content not only of the inactive but also of the active heterodimeric form of HGF, and this appeared to be due to the inhibition of the HGF degradation by gastric juice. CONCLUSION: Omeprazole-induced acceleration of gastric mucosal healing may be mediated at least in part by the reduced degradation of HGF in the stomach.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9586821&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effects on the cost and utilization of proton pump inhibitors from adding over-the counter omeprazole to drug benefit coverage in a state employee health plan.

Harris BN, West DS, Johnson J, Hong SH, Stowe CD.

University of Arkansas for Medical Sciences College of Pharmacy, Little Rock, Arkansas 72205-7199, USA. bnharris uams.edu

OBJECTIVE: To evaluate the financial effects in a state employee health plan of a change in the drug coverage policy to include over-the-counter (OTC) omeprazole in a tier-copayment drug benefit design that favored the OTC drug. METHODS: The policy change in the Arkansas State Employee Benefit Division (EBD) involved 2 principal parts: OTC omeprazole placed in a new OTC copayment tier (5 dollars) and an increase in pharmacy reimbursement to a 13 dollars dispensing fee for each OTC omeprazole prescription. The prescription claims database was used to examine utilization and cost data for beneficiaries who received prescriptions for a proton pump inhibitor (PPI) during the 2-month period (January and February 2004) preceding the change in policy to cover OTC omeprazole compared with the 2-month period following the policy change (March and April 2004). RESULTS: During the first week of the new policy (March 1-7, 2004), OTC omeprazole accounted for 47% of all PPI claims. From the third week through the end of the 2-month study period, OTC omeprazole represented 60% of PPI claims. This shift to OTC omeprazole from prescription PPIs produced EBD average savings of 40.86 dollars (40.5%) per PPI claim in the first 2 months after implementation of coverage of OTC omeprazole compared with the immediate previous 2-month period. The average copayment savings for EBD beneficiaries were 4.20 dollars (16.5%) per PPI claim. The average increase in pharmacy reimbursement was 118% (6.27 dollars per claim in the postperiod versus 2.88 dollars per claim in the preperiod). Despite a 17.2% increase in utilization as measured by days of PPI therapy per member per month (1.91 PMPM) in the postperiod versus 1.63 in the preperiod, EBD savings were 2.11 dollars (38.9%) PMPM. Based upon PMPM savings of 2.56 dollars in the second month of coverage of OTC omeprazole, annual savings would be about 3,978,240 dollars for average eligible membership of 129,500 in this state employee health plan. CONCLUSION: This policy change to include coverage of OTC omeprazole in the state employee drug benefit plan produced savings to the state of as much as 50% of the total cost of PPI drugs despite an apparent small increase in utilization of PPIs and an increase in pharmacy reimbursement of more than 100%. Plan beneficiaries realized significant savings on average for PPI drugs and particularly for each OTC omeprazole prescription.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15369428&dopt=Abstract omeprozole Prilosec