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The effect of antipyrine and rifampin on the metabolism of diazepam
Author(s) -
Ohnhaus E E,
Brockmeyer N,
Dylewicz P,
Habicht H
Publication year - 1987
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1987.125
Subject(s) - diazepam , metabolite , chemistry , pharmacology , desmethyl , metabolism , pharmacokinetics , excretion , medicine , biochemistry
The elimination of diazepam and antipyrine and the urinary excretion of their metabolites were investigated in 21 healthy volunteers before and after 7 days of administration of antipyrine, 1200 mg, and rifampin, 600 or 1200 mg. After administration of antipyrine and rifampin in two doses, antipyrine total body clearance increased by 53% and 60% or 98%, respectively. The clearance to metabolite showed a preferential induction of the norantipyrine pathway with different proportions after antipyrine and rifampin; rifampin, 1200 mg, also enhanced the 4‐hydroxyantipyrine pathway further. After antipyrine, diazepam total body clearance was increased by 102%, affecting all metabolic pathways to a similar extent. After rifampin in both doses, diazepam total body clearance rose equally to 300% and desmethyl‐ and 3‐hydroxydiazepam metabolic clearance to 400%. Therefore rifampin preferentially affects norantipyrine or desmethyl‐ and 3‐hydroxydiazepam metabolic formation, suggesting induction of different (iso)zymes of cytochrome P‐450. Clinical Pharmacology and Therapeutics (1987) 42, 148–156; doi: 10.1038/clpt.1987.125