Omeprazole metabolism

Andersson T, Regardh CG, Dahl-Puustinen ML, Bertilsson L. Slow omeprazole metabolizers are also poor S-mephenytoin hydroxylators. Ther Drug Monit 1990 12[4] 415-416. 

At neutral pH proton pump inhibitors are chemically stable, lipid-soluble, weak bases that have no inhibitory activity. In an acid environment they become protonated and a sulfenamide is formed. This sulfenamide binds covalently to the K+H+-ATPase proton pump in the gastric parietal cells, inhibiting this enzyme irreversibly and thus the entry of H+ ions into lumen. Omeprazole metabolizes at a pH of about 3.9. 1, whereas rabeprazole metabolizes at a pH of about 4.9. Secretion of acid only becomes possible again after new molecules of K+H+-ATPase are formed. 

Zhao and Lou [164] studied the metabolism of omeprazole to its two major metabolites, hydroxyomeprazole and omeprazole sulfone, in rat liver microsomes by a reversed-phase HPLC assay. The formation of metabolites of omeprazole depended on incubation time, substrate concentration, microsomal protein concentration, and was found to be optimal at pH 7.4. The Pmax and Km of omeprazole hydroxylation in the rat liver microsomal preparation were 2033 nmol /(min mg protein), and 46.8 ymol/l, respectively. The effects of seven drugs on omeprazole metabolism were tested. Mephenytoin, five benzodiazepines and pava-verine caused inhibition of omeprazole metabolism. 

Furuta T, Ohashi K, Kamata T, Takashima M, Kosuge K, Kawasaki T, Hanai H, Kubota T, Ishizaki T, Kaneko E. Effect of genetic differences in omeprazole metabolism on cure rates for Helicobacter pylori infection and peptic ulcer. Ann Intern Med 1998 129 1027-1030. 

Andersson T, Regardh CG, Lou YC, Zhang Y, Dahl ML, Bertilsson L. Polymorphic hydroxylation of S-mephenytoin and omeprazole metabolism in Caucasian and Chinese subjects. Pharmacogenetics 1992 2 25-31. 

Andersson T, Miners JO, Veronese ME, et al. Identification of human liver cyto-chrome-P450 isoforms mediating omeprazole metabolism. Br J Clin Pharmacol 1993 36 521-530. 

Gonzalez HM, Romero EM, Peregrina AA et al. (2003) CYP2C19- and CYP3A4-dependent omeprazole metabolism in west Mexicans. J Clin Pharmacol 43 1211-1215... 

Ishizaki T, Sohn DR, Kobayashi K et al. (1994) Interethnic differences in omeprazole metabolism in the two S-mephenytoin hydroxylation phenotypes studied in Caucasians and Orientals. Ther Drug Monit 16 214-215 Kanazawa H, Okada A, Matsushima Y et al. (2002) Determination of omeprazole and its metabolites in human plasma by liquid chromatography-mass spectrometry. J Chromatogr A 949 1-9... 

Svensson US, Ashton M, Trinh NH, Bertilsson L, Dinh XH, Nguyen VH, Nguyen TN, Nguyen DS, Lykkesfeldt J, Le DC. Artemisinin induces omeprazole metabolism in human beings. Clin Pharmacol Ther 1998 64(2) 160-7. 

Tateishi T, Kumai T, Watauabe M, Nakura H, Tauaka M, Kobayashi S. Ticlopidiue decreases the iu vivo activity of CYP2C19 as measured by omeprazole metabolism. Br J Cliu Pharmacol 1999 47(4) 454-7. 

Yoshiya G, Inoue Y, Kaneko S, Xateishi T., Different inhibitory effect of fluvoxamine on omeprazole metabolism between CYP2C19 genotypes, Br J Clin Pharmacol 2004 57(4) ... 

Andersson, T. Lagerstrom, P.-O. Miners, J.O. Veronese, M.E. Weidolf, L. Birkett, D.J. High-performance liquid chromatographic assay for human liver microsomal omeprazole metabolism. J.Chromatogr., 1993, 619, 291-297... 

At standard dosages, plasma elimination of omeprazole is fastest. Excretion occurs, to different proportions, by renal and faecal routes (Tab. 1). Omeprazole metabolism seems to be saturable, so that 40-mg doses of omeprazole and pantoprazole are excreted at the same rates (1.25 h) [22]. 

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