Omeprazole P450 effects

Shimatani, T., Inoue, M., Kuroiwa, T., et al. (2006) Acid-suppressive effects of rabeprazole, omeprazole, and lansoprazole at reduced and standard doses a crossover comparative study in homozygous extensive metabolizers of cytochrome P450 2C19. Clin. Pharmacol. Ther. 79, 144-152. 

Wenk M, Todesco L, Krahenbuhl S. Effect of St John s wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females. Br J Clin Pharmacol 2004 57(4) 495 99. Wang LS, Zhou G, Zhu B, et al. St John s wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omeprazole. Clin Pharmacol Therapeut 2004 75(3) 191-197. 

Li XQ, Andersson TB, Ahlstrom M, et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pan-toprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 2004 32 821-827. 

Lu C, Li AP (2001) Species comparison in P450 induction effects of dexamethasone, omeprazole and rifampin on P450 isoforms 1A and 3A in primary hepatocytes from man, Sprague-Dawley rat, minipig and beagle dog. Chem. Biol. Interact 134 271-281... 

Kim MJ, Bertino JS, Jr., Gaedigk A, Zhang Y, Sellers EM, Nafziger AN. Effect of sex and menstrual cycle phase on cytochrome P450 2C19 activity with omeprazole used as a biomarker. Clin Pharmacol Ther 2002 72 192-9. 

In hepatic microsomes, omeprazole inhibited cytochrome P450-mediated metabolic reactions in vitro. This effect was comparable to the inhibition caused by cimetidine with respect to the extent of the inhibitory effect and the effective concentrations [110]. Under well-defined clinical conditions, an... 

Adverse effects include nausea, headache, diarrhoea, constipation and rash but are uncommon. Omeprazole inhibits the 2C family of the cytochrome P450 system, decreasing the metabolism of warfarin, diazepam, carbamazepine and phenytoin, and enhancing the action of these drugs (but inhibition is less than with cimetidine). 

Most pharmaceutical companies and regulatory agencies discourage development of a P450 2C19 substrate because of potential problems for PM individuals. However, several studies indicate that PM patients may have more effective therapy (for ulcers) with omeprazole and related com-... 

Fluconazole and voriconazole almost certainly cause a rise in omeprazole and esomeprazole levels by inhibiting their metabolism by the cytochrome P450 isoenzymes CYP2C19 and CYP3A4. As esomeprazole is an inhibitor of and also a substrate for CYP2C19, it is likely to have the same effect as omeprazole. Ketoconazole only inhibits CYP3A4 and therefore causes a less marked rise in omeprazole levels. Itraconazole would be expected to interact similarly to ketoconazole. 

Cimetidine and omeprazole increase the gastric pH, which may lead to an increase in the absorption of proguanil. Cimetidine and omeprazole are also thought to inhibit the metabolism of proguanil, due to their inhibitory effects on cytochrome P450 isoenzyme CYP2C19. 

Itraconazole is a known potent inhibitor of the cytochrome P450 isoenzyme CYP3A4, but this isoenzyme is involved only in the metabolism of the less potent R-warfarin, and therefore inhibition would not be expected to have a marked effect on warfarin metabolism , (p.358). However, there appear to be no pharmacological studies to confirm this. Omeprazole (p.444) may also have had some minor part to play in the case described. ... 

Omeprazole may inhibit the oxidative metabolism of single doses of carbamazepine. However, when carbamazepine is taken continuously it induces its own metabolism by the cytochrome P450 isoenzyme CYP3A4, thereby possibly opposing the effects of this interaction. ... 

From the studies above it appears that grapefruit juice may have a minor inhibitory effect on the metabolism of omeprazole and lansoprazole by the cytochrome P450 isoenzyme CYP3A4 (which results in the sulphone metabolites). This was suggested to be due to intestinal inhibition of CYP3A4., Grapefruit juice does not affect the metabolism (hydroxyla-tion) of the proton pump inhibitors by CYP2C19. 

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