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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adult, Antidepressive Agents, Aryl Hydrocarbon Hydroxylases, Cross-Over Studies, Cytochrome P-450 CYP2C19, Cytochrome P-450 Enzyme Inhibitors, Cytochrome P-450 Enzyme System, Drug Interactions, Enzyme Inhibitors, Female, Homozygote, Humans, Hydroxylation, Inactivation, Metabolic, Male, Mixed Function Oxygenases, Moclobemide, Omeprazole.
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Is omeprazole hydroxylation inhibited by a single dose of moclobemide in homozygotic EM genotype for CYP2C19? Context: The pharmacokinetics of omeprazole and its metabolites in healthy subjects were evaluated to determine if a single dose of moclobemide inhibited CYP2C19 activity. Sixteen volunteers, of whom eight were extensive metabolizers (EM) and eight were poor metabolizers for CYP2C19, participated in two studies. Venous blood samples were collected for 24 h after oral ingestion of 40 mg omeprazole with or without 300 mg moclobemide coadministration. The pharmacokinetic change of omeprazole, omeprazole sulphone and 5-hydroxyomeprazole concentrations were assessed to test for an interaction between omeprazole and moclobemide. The coadministration of moclobemide in EMs approximately doubled the mean AUC (from 1834 to 3760 ng ml(-1) h) and C(max) (from 987 to 1649 ng ml(-1)) of omeprazole, and increased the AUC of omeprazole sulphone without changing AUC ratio of omeprazole to omeprazole sulphone. Moclobemide coadministration more than doubled the AUC ratio of omeprazole to 5-hydroxyomeprazole (from 2.5 to 5.3) in EMs, too. There was a significant decrease in Cmax and AUC of 5-hydroxyomeprazole in PMs but no significant changes were seen in the results for omeprazole and omeprazole sulphone AUCs.
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A single dose of moclobemide resulted in significant suppression of CYP2C19 activity in EMs. We conclude that physicians prescribing moclobemide should pay attention to its pharmacokinetic interactions even on the first day of coadministration with CYP2C19 substrates. Final Decision: yes