Induction of drug-metabolizing enzymes by tricyclic antidepressants in human liver: characterization and partial resolution of cytochromes P-450.
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.
D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000302:isolation & purification; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D000929:Antidepressive Agents, Tricyclic; D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System