Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms

J. W. Ko, N. Sukhova, D. Thacker, P. Chen, D. A. Flockhart

Research output: Contribution to journalArticle

Abstract

To compare the potency and specificity of omeprazole (OME) and lansoprazole (LAN) as inhibitors of cytochrome P450 isoforms, we performed human liver microsomal assays on CYP2C19 (S-mephenytoin 4-hydroxylation), CYP2C9 (tolbutamide 4-hydroxylation), CYP3A (dextromethorphan N-demethylation),CYP2D6(dextromethorphan O-demethylalion) and CYP1A2 (phenacetin O-deethylation). Both drugs were potent, competitive inhibitors of CYP2C19. For OME, the upper limit of 'window of selectivity' was at least 20 times greater than the Ki. While both drugs showed similar inhibitory effects on CYP2C9 and CYP3A, LAN showed at least 5 times more potent inhibition of CYP2D6. No inhibition of CYP1A2 was noted. Inhibitory constants(Ki ± SD, μM) were as follows: P450 isoforms OME LAN CYP2C19 3.1 ± 2.2 3.2 ± 1.3 CYP2C9 40.1 ± 14.8 52.1 ±1.4 CYP3A 84.4 ± 4.0 170.4 ± 7.1 CYP2D6 240.7 ± 102.0 44.7 ± 22.0 OME appears to be a useful, selective inhibitor of CYP2C19 because of its potency and broad 'window of selectivity'. While effects on other cytochrome P450 isoforms are similar, these data suggest that LAN may be the more important inhibitor of CYP2D6.

Original languageEnglish (US)
Pages (from-to)171
Number of pages1
JournalClinical Pharmacology and Therapeutics
Volume61
Issue number2
StatePublished - 1997
Externally publishedYes

Fingerprint

Lansoprazole
Omeprazole
Cytochrome P-450 CYP3A
Cytochrome P-450 CYP2D6
Cytochrome P-450 Enzyme System
Protein Isoforms
Dextromethorphan
Cytochrome P-450 CYP1A2
Hydroxylation
Mephenytoin
Phenacetin
Tolbutamide
Pharmaceutical Preparations
Liver
Cytochrome P-450 CYP2C9
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2C19

ASJC Scopus subject areas

  • Pharmacology

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. Clinical Pharmacology and Therapeutics, 61(2), 171.

Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. / Ko, J. W.; Sukhova, N.; Thacker, D.; Chen, P.; Flockhart, D. A.

In: Clinical Pharmacology and Therapeutics, Vol. 61, No. 2, 1997, p. 171.

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', Clinical Pharmacology and Therapeutics, vol. 61, no. 2, pp. 171.
Ko, J. W. ; Sukhova, N. ; Thacker, D. ; Chen, P. ; Flockhart, D. A. / Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. In: Clinical Pharmacology and Therapeutics. 1997 ; Vol. 61, No. 2. pp. 171.
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