Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms

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

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)853-862
Number of pages10
JournalDrug Metabolism and Disposition
Volume25
Issue number7
StatePublished - Jul 1997
Externally publishedYes

Fingerprint

Lansoprazole
Omeprazole
Cytochrome P-450 Enzyme System
Protein Isoforms
Dextromethorphan
Pharmaceutical Preparations
Dextrorphan
Mephenytoin
Drug interactions
Phenacetin
Cytochrome P-450 CYP1A2
Tolbutamide
Liver
Acetaminophen
Drug Interactions

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Ko, J. W., Sukhova, N., Thacker, D., Chen, P., & Flockhart, D. A. (1997). Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. Drug Metabolism and Disposition, 25(7), 853-862.

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, 07.1997, p. 853-862.

Research output: Contribution to journalArticle

Ko, JW, Sukhova, N, Thacker, D, Chen, P & Flockhart, DA 1997, 'Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms', Drug Metabolism and Disposition, vol. 25, no. 7, pp. 853-862.
Ko JW, Sukhova N, Thacker D, Chen P, Flockhart DA. Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. Drug Metabolism and Disposition. 1997 Jul;25(7):853-862.
Ko, Jae Wook ; Sukhova, Nadia ; Thacker, David ; Chen, Patricia ; Flockhart, David A. / Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. In: Drug Metabolism and Disposition. 1997 ; Vol. 25, No. 7. pp. 853-862.
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