title: The effect of antipyrine and rifampin on the metabolism of diazepam.
abstract: 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.
mesh_terms: D015065:17-Hydroxycorticosteroids / Q000378:metabolism; D000328:Adult; D000983:Antipyrine / Q000378:metabolism / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D012293:Rifampin / Q000494:pharmacology*
chemical_list: D015065:17-Hydroxycorticosteroids; C001380:6 beta-hydroxycortisol; D003975:Diazepam; D000983:Antipyrine; D012293:Rifampin; D006854:Hydrocortisone