Drugs online research references
Scand J Gastroenterol Suppl. 1986;118:99-104.
Pharmacokinetics and metabolism of omeprazole in man.
Regardh CG.
Four studies of the pharmacokinetics and metabolism of omeprazole are briefly discussed. Two of these were carried out in young healthy subjects and indicated that about 54% of an oral dose is available to the systemic circulation. The distribution of omeprazole after an intravenous dose was consistent with localization of a major fraction of the drug in the extracellular water, with about 25% restricted to the blood. Omeprazole was rapidly cleared and possessed the characteristics of a high clearance drug; insignificant amounts of 14C-omeprazole were excreted by the kidneys, though metabolites were excreted very rapidly. Six different metabolites were reported, the major one being hydroxy-omeprazole. Increasing the intravenous dose of omeprazole from 10 mg to 40 mg had no significant effect on the pharmacokinetic parameters determined. A study in patients with impaired renal function showed that this had little effect on the kinetics of omeprazole, though excretion of metabolites was significantly affected. A study of elderly healthy subjects suggested that the disposition characteristics of omeprazole are affected to some extent by age; further studies are needed to elucidate the clinical implications. Omeprazole has been reported to prolong the half-life of diazepam which may be due to inhibition of the demethylation of diazepam. The interaction of omeprazole with the kinetics of aminopyrine and antipyrine was much less pronounced.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3460172&dopt=Abstract
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Scand J Gastroenterol Suppl. 1985;108:79-94.
Pharmacokinetics and metabolism of omeprazole in animals and man--an overview.
Regardh CG, Gabrielsson M, Hoffman KJ, Lofberg I, Skanberg I.
The pharmacokinetics of omeprazole have been studied to varying extent in the mouse, rat, dog and in man. The drug is rapidly absorbed in all these species. The systemic availability is relatively high in the dog and in man provided the drug is protected from acidic degradation in the stomach. In man the fraction of the oral dose reaching the systemic circulation was found to increase from an average of 40.3 to 58.2% when the dose was raised from 10 to 40 mg, suggesting some dose-dependency in this parameter. The drug distributes rapidly to extra-vascular sites. The volume of distribution, V beta, in man is comparable to the volume of the extracellular water. The penetration into the red cells is low, the ratio between the concentration in whole blood and in plasma being about 0.6. Omeprazole is bound to about 95% to proteins in human plasma. The binding is lower in the dog and rat (90 and 87%, respectively). Omeprazole is eliminated almost completely by metabolism and no unchanged drug has been recovered in the urine in the species studied. Two metabolites, characterised as the sulfone and sulfide of omeprazole, have been identified and quantified in human plasma. The mean elimination half-life in man and in the dog is about 1 hour, whereas half-lives in the range of 5 to 15 minutes have been recorded in the mouse. In two studies in man, the mean total body clearance was 880 and 1097 ml X min-1, indicating that omeprazole belongs to the group of high clearance drugs. In the dog, too, the drug appears to be rapidly cleared from the blood, the mean total body clearance being about 10.5 ml X min-1 X kg-1. In the rat and dog, 20 to 30% of an i.v. or oral dose of omeprazole is excreted as metabolites in the urine and the remaining fraction is recovered in the faeces within three days after the administration. In man, the excretion of radioactivity via the kidneys is much more efficient and the recoveries in the excreta are approximately the reverse of those in the rat and dog. In vitro studies with rat liver microsome preparations suggest that omeprazole and cimetidine inhibit cytochrome P-450-mediated metabolic reactions to about the same extent in equimolar concentrations. However, since the molar daily dose of cimetidine will be 25 to 50 times higher than that of omeprazole, the latter might have less influence on the mixed function oxidase system than cimetidine.(ABSTRACT TRUNCATED AT 400 WORDS)
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3858978&dopt=Abstract
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Clin Pharmacol Ther. 1994 Apr;55(4):402-11.
Accelerated caffeine metabolism after omeprazole treatment is indicated by urinary metabolite ratios: coincidence with plasma clearance and breath test.
Rost KL, Roots I.
Institute of Clinical Pharmacology, Klinikum Steglitz, Free University of Berlin, Germany.
BACKGROUND: Omeprazole has previously been shown to induce hepatic cytochrome P4501A2 activity, as evidenced by an accelerated N-3-demethylation in the 13C-[N-3-methyl]-caffeine breath test. In this study we investigated whether the inducing potency of omeprazole can be quantified by the determination of urinary caffeine metabolite ratios, which are based on the urinary excretion of N-3-demethylated metabolites. These data were also compared with changes in plasma clearance. METHODS: Twelve healthy volunteers were phenotyped as extensive metabolizers of S-mephenytoin and received seven daily doses of 40 mg omeprazole; eight of these were also treated with 120 mg/day. Moreover, six poor metabolizers were treated with 40 mg/day omeprazole. Three different urinary caffeine metabolite ratios were evaluated from urine samples collected between 5 and 8 hours after caffeine intake. RESULTS: The extensive metabolizers had a slight and nonsignificant acceleration between 7.8% and 17.0% after 40 mg omeprazole by the urinary ratios. However, treatment with 120 mg/day led to highly significant increases ranging from 25.0% to 32.1% (p < 0.002) in this group. Poor metabolizers responded with the highest increases of 40.2% to 41.2%. There was a good correlation between these parameters and the caffeine breath test, as well as the plasma caffeine clearance. CONCLUSION: The study showed an equivalent caffeine N-3-demethylation activity by all evaluation methods. The three urinary caffeine metabolite ratios sampled at the convenient interval of 5 to 8 hours after administration showed the dependence of CYP1A2 induction by omeprazole on the dose and genetic trait of S-mephenytoin hydroxylase.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8162667&dopt=Abstract
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