Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms

Jae Wook Ko, Nadia Sukhova, David Thacker, Patricia Chen, David A. Flockhart

195 Scopus citations


The human clearance of omeprazole and lansoprazole is conducted primarily by the hepatic cytochrome P450 (CYP) system. Efficacy data indicate few differences between these two drugs, but they may exhibit discrete drug interaction profiles. To compare the potency and specificity of these drugs as inhibitors of CYP isoforms, we performed in vitro studies with human liver microsomal preparations. Both drugs were potent, competitive inhibitors of CYP2C19, as measured by the conversion of S-mephenytoin to 4- hydroxymephenytoin (k1 = 3.1 ± 2.2 μM for omeprazole, K1 = 3.2 ± 1.3 μM for lansoprazole). For omeprazole, the highest concentration at which >70% inhibition of CYP2C19 was observed with no significant inhibitory effect on other isoforms was at least 20 times greater than K1. Both drugs were competitive inhibitors of CYP2C9-catalyzed conversion of tolbutamide to 4- hydroxytolbutamide (K1 = 40.1 ± 14.8 μM for omeprazole, K1 = 52.1 ± 1.4 μM for lansoprazole) and were noncompetitive inhibitors of CYP3A-catalyzed conversion of dextromethorphan to 3-methoxymorphinan (K1 = 84.4 ± 4.0 μM for omeprazole, K1 = 170.4 ± 7.1 μM for lansoprazole). Lansoprazole was at least 5 times more potent (K1 = 44.7 ± 22.0 μM) than omeprazole (k1 = 240.7 ± 102.0 μM) as an inhibitor of CYP2D6-mediated conversion of dextromethorphan to dextrorphan. No inhibition of CYP1A2, assessed by measuring the conversion of phenacetin to acetaminophen, was noted. Our data suggest that whereas the inhibitory profiles of these two drugs are similar, lansoprazole may be the more important in vitro inhibitor of CYP2D6. Since its inhibition is very potent and has a broad 'window of selectivity,' omeprazole seems to be a useful, selective inhibitor of CYP2C19.


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Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. / Ko, Jae Wook; Sukhova, Nadia; Thacker, David; Chen, Patricia; Flockhart, David A.

In: Drug Metabolism and Disposition, Vol. 25, No. 7, 01.07.1997, p. 853-862.

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