The effect of antipyrine and rifampin on the metabolism of diazepam

Clin Pharmacol Ther. 1987 Aug;42(2):148-56. doi: 10.1038/clpt.1987.125.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 17-Hydroxycorticosteroids / metabolism
  • Adult
  • Antipyrine / metabolism
  • Antipyrine / pharmacology*
  • Diazepam / metabolism*
  • Endoplasmic Reticulum / enzymology
  • Humans
  • Hydrocortisone / analogs & derivatives
  • Hydrocortisone / metabolism
  • Kinetics
  • Male
  • Microsomes, Liver / enzymology
  • Rifampin / pharmacology*


  • 17-Hydroxycorticosteroids
  • 6 beta-hydroxycortisol
  • Diazepam
  • Antipyrine
  • Rifampin
  • Hydrocortisone