omeprazole, Prilosec
Artemisinin induces omeprazole metabolism in human beings.

Svensson US, Ashton M, Trinh NH, Bertilsson L, Dinh XH, Nguyen VH, Nguyen TN, Nguyen DS, Lykkesfeldt J, Le DC.

Department of Pharmacy, Uppsala University, Sweden.

OBJECTIVE: This study investigated whether time-dependent artemisinin pharmacokinetics correlated to CYP3A4 or CYP2C19 activity in vivo. METHODS: Artemisinin (two oral doses per day of 250 mg) was given to nine healthy Vietnamese subjects for 7 days (day 1 to day 7). Single 20 mg doses of omeprazole were given orally on day -7, day 1, and day 7. Single doses of artemisinin and omeprazole were given in combination on day 14 after a 6-day washout period. The pharmacokinetics of artemisinin, omeprazole, hydroxyomeprazole, and omeprazole sulfone were evaluated on days -7, 1, 7, and 14. On the same days urine was collected for the determination of 6beta-hydroxycortisol and cortisol excretion. RESULTS: Areas under plasma concentration-time curves (AUC) for artemisinin and omeprazole decreased on day 7 to 20% (95% confidence intervals, 13%, 28%) and 35% (25%, 46%), respectively, compared with values on day 1. AUC ratios for hydroxyomeprazole/omeprazole increased 2.2-fold (1.7, 2.7) on day 7 compared with values on day 1. All values were normalized at day 14. There were no significant changes in the omeprazole sulfone/omeprazole ratio or in the 6beta-hydroxycortisol/cortisol ratio between the study days. In one subject found to have poor CYP2C19 metabolization, the elimination of omeprazole increased after artemisinin exposure, with no change in the hydroxyomeprazole/omeprazole AUC ratio. CONCLUSION: Artemisinin did not alter CYP3A4 activity, whereas an increase in CYP2C19 activity was observed. The increased elimination of omeprazole in both poor and extensive CYP2C19 metabolizers suggests artemisinin induces both CYP2C19 and another enzyme.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9728896&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of L-lactic acid on calcium absorption in rats fed omeprazole.

Chonan O, Takahashi R, Yasui H, Watanuki M.

Yakult Central Institute for Microbiological Research, Tokyo, Japan.

We examined the effect of L-lactic acid on calcium absorption in male Wistar rats made achlorhydric by dietary omeprazole, a proton pump inhibitor. The dietary omeprazole intake (0.03 g/100 g of diet) increased the gastric pH and decreased the apparent calcium absorption ratio. Dietary famotidine (0.03 g/100 g of diet), an H2-receptor antagonist, and lower doses of omeprazole (0.005 or 0.01 g/100 g of diet) did not affect the gastric pH or the calcium absorption. In a second experiment, dietary lactic acid (0.5, 1.0, or 2.5 g/100 g of diet) increased the intestinal calcium absorption dose dependently in rats fed omeprazole (0.03 g/100 g of diet). The gastric pH was significantly decreased only in the rats fed higher doses of lactic acid (1.0, or 2.5 g/100 g of diet). In a third experiment, a dietary sour milk beverage containing lactic acid (0.5 g/100 g of diet) increased the intestinal calcium absorption, but did not affect the gastric pH in rats fed omeprazole (0.03 g/100 g of diet). Although the significance of gastric acid in terms of overall calcium absorption is not known, under the present experimental conditions, the inhibition of gastric acid secretion by dietary omeprazole decreased the apparent calcium absorption, and the dietary lactic acid prevented the calcium absorption in rats fed omeprazole.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9742467&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Does hormone therapy increase allergic reactions and upper gastrointestinal problems? Results from a population-based study of Swedish woman. The women's health in the Lund area (WHILA) study.

Khatibi E A, Samsioe G, Li C, Lidfeldbt J, Agardh CD, Nerbrand C; Women's health in the Lund area study.

Department of Obstetrics and Gynaecology, Lund University Hospital, Lund S-221 85, Sweden.

OBJECTIVES: To delineate the use of various drugs particularly pertaining to allergy and upper gastrointestinal problems in relation to hormone status in middle aged women. METHODS: An analysis from a population-based study on women born between 1935 and 1945 and lived in the Lund area southern Sweden. Of 10,766 women, 6,917 provided complete data sets; in turn 5,673 were assessed for the use of medication in this study. Among the cohort, 9% of women were premenopausal (PM), 54% were postmenopausal without hormone replacement therapy (PM0) and 37% were current hormone replacement therapy users (PMT). RESULTS: There were 7 (1.3%) women in PM, 11 (0.4%) in PM0 and 21 (1.0%) in PMT group who used loratadine regularly. There was a significant difference between the PM and PM0 groups and also between the PM0 and PMT groups in the use of loratadine (P < 0.05 ). Among 21 loratadine users in PMT group 4 (19%) used transdermal patches and 17 (81%) used oral HRT. The result for omeprazole use was as follows: 4 (0.8%) of PM group, 39 (1.3%) of PM0 group and 42 (2.0%) of PMT group. The use of omeprazole was significantly higher in the PMT group than in the PM (P = 0.05 ) and PM0 group (P < 0.05 ). There was no relation between the use of omeprazole and smoking or alcohol consumption. CONCLUSIONS: Use of hormone replacement therapy seems to be related to a higher frequency of omeprazole and loratadine use, which implies that hormone replacement therapy, may be associated with more upper gastrointestinal symptoms as well as allergy.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15283937&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Induction of cytochrome P-450 1A1 by omeprazole in human HepG2 cells is protein tyrosine kinase-dependent and is not inhibited by alpha-naphthoflavone.

Kikuchi H, Hossain A, Yoshida H, Kobayashi S.

Research Institute of Development, Aging and Cancer, Tohoku University, Sendai, 980-8575, Japan. hkikuchi idac.tohoku.ac.jp

Benzimidazole compounds, such as omeprazole and thiabendazole, are a different type of CYP1A1 inducer from Ah receptor-ligands, such as TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) and 3-methylcholanthrene. In HepG2 cells, the commonly used tyrosine kinase inhibitors, herbimycin-A and a series of tyrphostins, inhibited the induction of CYP1A1 produced by treatment with TCDD. Genistein, another type of tyrosine kinase inhibitor, inhibited the induction of CYP1A1 whether it was produced by omeprazole or TCDD; however, this inhibition was caused by a dual effect of genistein, that is an anti-tyrosine kinase and an anti-topoisomerase I effect. An antagonist of Ah receptor, alpha-naphthoflavone (0.1-10 microM), and 3'-methoxy-4'-aminoflavone (1 microM), did not inhibit the induction of CYP1A1 produced in HepG2 cells by omeprazole, but both of them did inhibit that produced by TCDD. In one of a number of human lung tumor cell lines, S6T, the inducibility of CYP1A1 was high by TCDD, whereas the inducibility by omeprazole was low. Thus, omeprazole appears to induce CYP1A1 by initiating a protein tyrosine kinase-mediated signal transduction pathway, a different pathway from that inhibited by TCDD. Copyright 1998 Academic Press.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9784250&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Omeprazole is more effective than famotidine for preventing acute gastritis in rats.

Topaloglu U, Muftuoglu T, Akturk Z, Ekinci H, Peker O, Unalmiser S.

Department of General Surgery, Haydarpasa Teaching Hospital, Kadikoy, Uskudar, Istanbul, Turkey.

PURPOSE: Acute gastric mucosal lesions, which can develop within a few hours after polytrauma, shock, major operations, central nervous system lesions, or severe infection, cause about 33% of cases of gastrointestinal bleeding. We analyzed and compared the effectiveness of famotidine and omeprazole on acute gastric mucosal lesions. METHODS: Thirty male albino Wistar rats were given ketalar anesthesia after 12 h fasting, then immobilized and exposed to stress according to Brodie's protocol, without restricting their respiration. We divided the rats into three groups of ten according to whether they were given famotidine, omeprazole, or normal saline (control group). All rats were ulcer-indexed according to the diameter of their ulcers. The stomach contents were aspirated for acid output and pH analysis, and sent to the laboratory. The total number of mast cells was also counted. RESULTS: Omeprazole was more effective than famotidine in keeping gastric pH high and lowering the total gastric acid output. Lower ulcer indexes in acute gastric mucosal erosions and better protected mucosal integrity were found in the omeprazole-treated rats. CONCLUSION: Omeprazole prevents acute gastric mucosal erosions in rats more effectively than famotidine.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15290400&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Effect of omeprazole on gastric bicarbonate secretion in patients with duodenal ulcer.

Singh K, Nain CK, Singh V.

Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh.

BACKGROUND: Omeprazole, a H+/K+ ATPase inhibitor, has been shown to reduce gastric bicarbonate secretion in cats. However, there has been no study on the effect of omeprazole on bicarbonate secretion in patients with duodenal ulcer (DU). METHODS: Fifteen men with duodenal ulcer (mean age 38 years, range 22-57) were included. Baseline gastric acid output, bicarbonate secretion, and parietal and nonparietal secretions were estimated before and after omeprazole therapy (20 mg/day) for four weeks. RESULTS: Omeprazole administration did not significantly alter bicarbonate secretion (3.3 [1.2] vs 2.4 [0.4] mmol/h), though there was significant reduction in gastric acidity (44.2 [6.6] vs 20.7 [4.6] mmol/L, p < 0.01). CONCLUSION: Omeprazole reduces acid secretion but does not affect gastric bicarbonate secretion in patients with DU.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9795500&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
Bantu Tanzanians have a decreased capacity to metabolize omeprazole and mephenytoin in relation to their CYP2C19 genotype.

Herrlin K, Massele AY, Jande M, Alm C, Tybring G, Abdi YA, Wennerholm A, Johansson I, Dahl ML, Bertilsson L, Gustafsson LL.

Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Huddinge University Hospital, Sweden.

OBJECTIVE: To investigate the CYP2C19 polymorphism in Tanzanians because this enzyme shows large interindividual differences in activity and metabolizes several drugs of importance in Africa, especially the antimalarial agent chloroguanide (INN, proguanil). METHODS: Two hundred fifty-one Tanzanian healthy volunteers were phenotyped with respect to CYP2C19 with use of a single oral dose of mephenytoin (n = 106), a single oral dose of omeprazole (n = 207), or both. Sixty-two were phenotyped with both probe drugs. The urinary 0- to 8-hour S/R-mephenytoin ratio and the plasma omeprazole metabolic ratio (MR) (omeprazole/hydroxyomeprazole) 3 hours after drug intake were determined. The genotype was determined by analysis for CYP2C19*1 (wt), CYP2C19*2 (m1), and CYP2C19*3 (m2). Ten subjects with high omeprazole MR were screened for new mutations in the CYP2C19 gene by searching for single-strand conformation polymorphisms (SSCP). RESULTS: Eight subjects were classified as mephenytoin poor metabolizers (7.5%). Only 5 of these were homozygous for mutated alleles. The S/R ratio was skewed to the right (lower CYP2C19 activity) compared with other ethnic groups studied previously. No new mutations were found with polymerase chain reaction (PCR)-SSCP. We found 30 volunteers (14.5%) with an MR > 7, which is the antimode found previously in white subjects and Asian subjects. Of the 251 volunteers genotyped, 3.2% were homozygous for mutated alleles and 66.1% were homozygous for the wild-type allele. The allele frequencies of CYP2C19*1, *2, and *3 were 81.5%, 17.9%, and 0.6%, respectively. The correlation between the S/R-mephenytoin ratio and the omeprazole MR was significant (Spearman r = 0.59; P < .01). CONCLUSION: Tanzanians have a decreased capacity to metabolize both omeprazole and mephenytoin when their genotype is compared with metabolic capacity and genotype in other previously studied populations. We identified a low frequency of the Asian allele (CYP2C19*3). Although we did not find any new mutations, our results may be consistent with the presence of yet-unidentified mutations of CYP2C19 that causes decreased CYP2C19 activity in the Tanzanian population.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9797796&dopt=Abstract omeprozole Prilosec



omeprazole, Prilosec
A simple high performance liquid chromatography assay for simultaneous determination of omeprazole and metronidazole in human plasma and gastric fluid.

Yeung PK, Little R, Jiang Y, Buckley SJ, Pollak PT, Kapoor H, Veldhuyzen van Zanten SJ.

Pharmacokinetics and Metabolism Laboratory, College of Pharmacy, Dalhousie University, Halifax, N.S., Canada.

Antibiotics which are actively secreted into gastric fluid may be more efficacious in the eradication of Helicobacter pylori in peptic ulcer disease. Other agents used in the treatment of this disease such as omeprazole or other anti-secretory agents may alter the secretion and/or distribution characteristics of antibiotics. In order to test the applicability of these concepts to metronidazole, a sensitive and specific high performance liquid chromatography (HPLC) assay was developed to quantitate omeprazole in plasma, and metronidazole in plasma and gastric fluid. The HPLC system consisted of a multi-phase column combining anion exchange and reversed phase separation (OmniPac Pax-500, Dionex), and a variable wavelength UV detector set at 254 nm. The mobile phase was a mixture of 0.1 M sodium phosphate buffer:methanol:acetonitrile (60:20:20) with final pH adjusted to approximately 7.0. Metronidazole and omeprazole were extracted by adsorption onto a C2-bonded silica gel solid phase extraction column, and eluted with methanol. The extract was dried, reconstituted in a solution of acetyl salicylic acid (ASA), and then injected into the HPLC system. Under these conditions, metronidazole, omeprazole and ASA were well separated and recoveries in plasma were greater than 80%. Omeprazole could not be measured in gastric fluid because of rapid decomposition. Using 0.3 ml of sample, the assay sensitivity was less than 0.1 microgram ml-1 and linear up to 10 micrograms ml-1. Both intra- and inter-assay CV were greater than 15%. It was applied successfully in determining metronidazole concentrations in clinical samples of plasma and gastric fluid.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9800658&dopt=Abstract omeprozole Prilosec