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Induction of drug‐metabolizing enzymes by tricyclic antidepressants in human liver: characterization and partial resolution of cytochromes P‐ 450.
Author(s) -
Cresteil T,
Celier C,
Kremers P,
Flinois JP,
Beaune P,
Leroux JP
Publication year - 1983
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1983.tb02236.x
Subject(s) - chemistry , benzphetamine , tricyclic , pharmacology , biochemistry , microsome , enzyme , stereochemistry , medicine
Drug‐metabolizing enzyme activities were determined in liver microsomes from six kidney‐transplant donors, one tricyclic antidepressant‐treated and five untreated donors. The tricyclic antidepressant treatment modifies neither the overall cytochrome P‐450 content of the liver, nor enzymatic activities of 4‐nitroanisole demethylase, aniline hydroxylase, epoxide hydrolase and glutathione S‐transferase. Only benzphetamine and ketotifen demethylation and conjugation of bilirubin with UDP‐glucuronic acid are markedly augmented (more than two‐fold). Separation of the different cytochrome P‐450 fractions on a DEAE cellulose column indicates a modification of the elution pattern: the fraction increased by tricyclic antidepressants is responsible for the enhanced monooxygenase activity towards benzopyrene and benzphetamine.