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Omeprazole and aryl hydrocarbon hydroxylases: Should we be worried?
Author(s) -
Kolars J. C.,
Turgeon D. K.,
Watkins P. B.
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840130131
Subject(s) - omeprazole , microsome , chemistry , acetaminophen , enzyme , phenacetin , cytochrome p450 , enzyme inducer , inducer , in vitro , cyp3a , cytochrome , pharmacology , biochemistry , medicine , biology , chromatography , gene
Diaz and colleagues have carefully studied the effects of omeprazole on the expression of cytochrome P‐450 in primary cultures of human hepatocytes. When omeprazole was added to the culture medium in varying concentrations, there was an increase in P‐450IA2 protein and mRNA concentrations, an increase in de novo synthesis of P‐450IA2 protein, and an increase in microsomal catalytic activities characteristic of P‐450IA2 (phenacetin deethylase and acetanilide hydroxylase). Omeprazole treatment also resulted in an increase in both enzymatic activity characteristic of P‐450IA1 (ethoxyresorufin deethylase and benzpyrene hydroxylase) and concentration of P‐450IA1 mRNA. In contrast, omeprazole appeared to have no significant effect on expression of other P‐450s within the P‐450II or P‐450III families in the hepatocytes. To validate these in vitro observations, liver biopsy specimens were obtained from five patients before and after a 4‐day course of pharmacological doses of omeprazole. In each patient, omeprazole treatment appeared to result in a two‐ to eightfold increase in P‐450IA2 immunoreactive protein and P‐450IA1 and P‐450IA2 enzymatic activities. The authors conclude that omeprazole is an inducer of P‐450IA2 and probably P‐450IA1 in human liver. Induction of these enzymes could potentiate the bioactivation of carcinogens or the hepatotoxicity of some drugs such as acetaminophen.