omeprazole, Prilosec
Antacid provides better restoration of glandular structures within the gastric ulcer scar than omeprazole.

Schmassmann A, Tarnawski A, Gerber HA, Flogerzi B, Sanner M, Varga L, Halter F.

Gastrointestinal Unit, University Hospital, Inselspital, Bern, Switzerland.

Mucosa of healed gastric ulcers displays histological abnormalities that are possibly the basis of ulcer recurrence. The influence of antacid and omeprazole treatment was studied on the quality of ulcer healing. Sixty four rats with gastric cryoulcers were treated daily either with placebo, antacid, omeprazole, or antacid plus omeprazole. Ulcer size was measured three times per week with a novel video endoscopic method. Prostaglandin generation (day 6), cell proliferation (day 8 and 15), height and cell composition of ulcer margin (day 8), and mucosal scar (day 15) were quantitatively assessed. Antacid, omeprazole, and antacid plus omeprazole significantly accelerated ulcer healing predominantly during days 3-8. Compared with placebo, the height of ulcer margin and mucosal ulcer scar was significantly increased in antacid (+7 and +9% respectively) and significantly decreased in omeprazole (-33 and -22% respectively) and antacid plus omeprazole (-26 and -18% respectively) treated rats. The number of bromodeoxyuridine labelled cells (+42%, day 8), epithelial cell mass (+42%, day 15), and the ratios of epithelial cells/connective tissue (+73%, day 15) and epithelial cells/gland lumen (+100%, day 15) were significantly increased in antacid treated rats. In conclusion, both antacid and omeprazole accelerate ulcer healing but antacid provides a better quality of healing. This advantage is lost by cotreatment with omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8063216&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Intracellular binding is an important determinant of the avid hepatic uptake of the high clearance drug omeprazole.

Sewell RB, Brook CW, Mihaly GW, Morgan DJ, Smallwood RA.

Gastroenterology Unit, Austin Hospital, Melbourne, Victoria, Australia.

The contribution of intracellular storage to hepatic uptake of the high clearance drug, omeprazole, was examined in the recirculating isolated perfused rat liver preparation. Following injection of [3H]omeprazole (7.5 microCi, 5 mg) into the portal vein over 1 min, livers were perfused for 5 min (N = 3) or 30 min (N = 3) and then homogenized at 4 degrees and fractionated by differential centrifugation. Radiolabelled omeprazole and metabolites were determined by scintillation counting of fractions of eluant from HPLC. Seventy per cent of drug had been taken up by the liver at 5 min and 85% at 30 min, with unchanged drug representing 43 and 7.4%, respectively, of drug taken up. At both times, 70-75% of intracellular unchanged drug and the major metabolites were located in the cytosol, and the cytosol:perfusate concentration ratio was approximately 10:1. Mitochondrial, lysosomal and microsomal fractions contained relatively little drug. Extensive cytosolic binding of omeprazole therefore contributes substantially to the initial avid hepatic first-pass uptake of this drug.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8080458&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole use at an urban county teaching hospital.

Brandhagen DJ, Pheley AM, Onstad GR, Freeman ML, Lurie N.

Department of Medicine, Hennepin County Medical Center, Minneapolis, MN 55415, USA.

To determine the appropriateness of use of omeprazole, all outpatient prescriptions over one year from a single county hospital pharmacy were analyzed. Appropriateness of omeprazole use was assessed by literature review and expert opinion. Two hundred twenty-one prescriptions were evaluated; 112 (56%) were inappropriate. Women received more inappropriate prescriptions (61% vs 44%, p = 0.01) and received endoscopy less frequently (52% vs 71%, p < 0.02) than did men. When age, gender, and prescribing clinic were examined as predictors of inappropriate use, only gender was significant (OR = 2.01, 95% CI = 1.52-2.66). This study, from a single institution, showed a high rate of inappropriate omeprazole use.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8523155&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Phenocopies of poor metabolizers of omeprazole caused by liver disease and drug treatment.

Rost KL, Brockmoller J, Esdorn F, Roots I.

Institute of Clinical Pharmacology, Universitatsklinikum Benjamin Franklin, Berlin, Germany.

BACKGROUND/AIMS: The kinetics of omeprazole and its primary metabolites 5'-hydroxyomeprazole and omeprazole sulfone were studied in healthy volunteers to evaluate omeprazole as a probe drug for the S-mephenytoin hydroxylase (CYP2C19) polymorphism. The plasma metabolic ratio obtained from the concentrations of omeprazole plus omeprazole sulfone over 5'-hydroxyomeprazole was investigated. METHODS: The time course of the omeprazole metabolic ratio was studied in 14 extensive metabolizers, one intermediate, and five poor metabolizers of CYP2C19 after a 1-week administration of 40 mg/d omeprazole. The ratio was then determined in 187 randomly selected Caucasian hospital patients and analyzed according to liver disease and co-medication. RESULTS: Between 1 and 4 h after omeprazole intake, the volunteers phenotyped by the urinary S/R-mephenytoin ratio were reliably identified as extensive metabolizers and poor metabolizers by an omeprazole metabolic ratio-antimode of 12. This antimode remained valid in eight extensive metabolizers and one poor metabolizer, who were re-investigated with 60 mg omeprazole b.i.d. for one week. Among 30 patients without concomitant drug intake, only one poor metabolizer (3.3%) was identified by both the S/R-mephenytoin ratio and omeprazole metabolic ratio. However, 30 of 47 patients with liver disease and 20 of 110 co-medicated patients without liver disease had a ratio > 12. This highly exceeded the poor metabolizer frequency of 3-4% in Caucasians. CONCLUSIONS: Like other phenotypic tests, the omeprazole metabolic ratio appears to reflect CYP2C19 genotype reliably only in individuals without liver disease or co-medication. The omeprazole metabolic ratio may serve the double purpose of phenotyping for CYP2C19 and to individualize dosing in omeprazole-treated patients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8550990&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole.

Yin OQ, Tomlinson B, Waye MM, Chow AH, Chow MS.

School of Pharmacy, the Chinese University of Hong Kong, Shatin, New Territories, Hong Kong.

OBJECTIVE: Ginkgo biloba was found to exert a significant inductive effect on CYP2C19 activity. This study was designed to investigate the potential herb-drug interaction between G. biloba and omeprazole, a widely used CYP2C19 substrate, in subjects with different CYP2C19 genotypes. METHODS: Eighteen healthy Chinese subjects previously genotyped for CYP2C19 were selected. All subjects received a single omeprazole 40 mg at baseline and then at the end of a 12-day treatment period with G. biloba (140 mg, bid). Multiple blood samples were collected over 12 h, and 24 h urine was collected post omeprazole dosing. Plasma and urine concentrations of omeprazole and its metabolites, 5-hydroxyomeprazole and omeprazole sulfone, were determined, and their pharmacokinetics calculated non-compartmentally. RESULTS: Plasma concentrations of omeprazole and omeprazole sulfone were significantly decreased, and 5-hydroxyomeprazole significantly increased following G. biloba administration in comparison to baseline. A significant decrease in the ratio of area under the plasma concentration-time curve (AUC) of omeprazole to 5-hydroxyomeprazole was observed in the homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers, respectively. The decrease was greater in PMs than EMs. No significant changes in the AUC ratios of omeprazole to omeprazole sulfone were observed. Renal clearance of 5-hydroxyomeprazole was significantly decreased after G. biloba, but the change was not significantly different among the three genotype groups. CONCLUSION: Our results show that G biloba can induce omeprazole hydroxylation in a CYP2C19 genotype-dependent manner and concurrently reduce the renal clearance of 5-hydroxyomeprazole. Co-administration of G. biloba with omeprazole or other CYP2C19 substrates may significantly reduce their effect, but further studies are warranted.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15608563&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
[Effect of omeprazole administration on pancreatic content of enzymes in rats]

[Article in Portuguese]

Montagnini AL, Kubrusly MS, Coelho AM, Molan NA, da Cunha JE, Machado MC, Pinotti HW.

Departamento de Gastroenterologia, Faculdade de Medicina, Universidade de Sao Paulo.

Gastric chloride acid plays an important role in pancreatic enzyme synthesis and secretion, mediated by cholecystokinin released in the duodenum. This study was designed to evaluate the influence of gastric acid suppression by omeprazole on pancreatic enzyme content. Eighteen male Wistar rats (180-220 g) were divided in two groups: I--control and II--omeprazole. Animals received by intraduodenal catheter 3 doses of 0.5 ml saline solution (NaCl 0.9%)--Group I or 5 mumol/Kg of omeprazole solution--Group II at 24 h intervals. All animals, after an overnight fasting period, were killed 3 h after the last dose. Serum amylase and pancreatic tissue content of protein, trypsinogen, elastase, lipase and phospholipase A2 were determinated. Omeprazole treated animals (group II) showed statistically significant lower levels of serum amylase and pancreatic trypsinogen content (P < 0.05). We believe that this effect is related with acid secretion suppression by omeprazole and that it may be mediated by cholecystokinin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8578092&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Sucralfate affects the susceptibility of Helicobacter pylori to antimicrobial agents.

Slomiany BL, Piotrowski J, Majka J, Slomiany A.

Research Center, University of Medicine and Dentistry of New Jersey, Newark, USA.

BACKGROUND: Infection with Helicobacter pylori is regarded as a primary factor in the pathogenesis of gastric disease, and successful therapies now include a combination of antiulcer drugs with antimicrobial agents. In this study, we investigated the effect of sucralfate and omeprazole on the vitro anti-H. pylori activity of metronidazole, erythromycin, tetracycline, and amoxycillin. METHODS: Aliquots of H. pylori culture were transferred to the wells containing different concentrations of antibiotics either alone or in the presence of various doses of sucralfate and omeprazole and incubated for 3 days for MIC evaluation. RESULTS: The assays in the absence of sucralfate and omeprazole gave MIC value 0.10 mg/l for erythromycin, 0.12 mg/l for amoxycillin, 0.15 mg/l for tetracycline, and 14 mg/l for metronidazole. Inclusion of sucralfate evoked a 28% enhancement in the MIC of metronidazole, 2.5-fold in tetracycline, 8-fold in erythromycin, and 2-fold in amoxycillin. In the presence of omeprazole, the MIC of erythromycin improved 4-fold, tetracycline 1.6-fold, and amoxycillin, 2-fold. CONCLUSIONS: The results demonstrate that sucralfate enhances the anti-H. pylori activity of antibiotics and that this effect is comparable to that of omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8578215&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole has no effect on acetaminophen kinetics in the rat.

Melzer E, Lang A, Gopher A, Almog S, Ezra D, Bar-Meir S.

Gastroenterology Department, Sheba Medical Center, Tel Hashomer, Israel.

We investigated in the rat the effect of the H+/H(+)-ATPase inhibitor, omeprazole, on the kinetics of acetaminophen. Two groups of rats were treated with either omeprazole 50 mg/kg/day or the vehicle for 7 days. On day seven, the pharmacokinetic parameters of acetaminophen clearance were determined in the conscious rat. Elimination rate constant, elimination half life time, clearance and volume of distribution of acetaminophen were not disturbed by omeprazole. It is concluded that in the rat, omeprazole does not affect acetaminophen kinetics and, therefore, will not increase susceptibility to acetaminophen toxicity.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8582437&dopt=Abstract omeprozole Prilosec