Induction of hepatic microsomal enzymes after brief administration of rifampicin in man

Gastroenterology. 1977 May;72(5 Pt 1):924-6.

Abstract

The inducing effect of rifampicin (600 mg per day) on the hepatic microsomal drug-metabolizing system has been studied in 7 patients with normal liver after 6 days of oral administration. Using the plasma disappearance rate of antipyrine (15 mg per kg of body weight) as an index of liver microsomal metabolism, a significant decrease in the half-life of antipyrine has been observed: 11.7 +/- (1 sd) 4.7 hr before treatment as compared to 6.9 +/- 2.3 hr on the 7th day. Concomitantly, the half-life of rifampicin was 5.3 +/- 2.1 and 2.7 +/- 0.8 hr on the 1st and 7th day, respectively. These results demonstrate that rifampicin administration for only 6 days leads to the induction of the microsomal mixed function oxidase system in liver. These data are in agreement with the recent hypothesis that rifampicin may play a role in the hepatotoxicity of isoniazid by enhancing its microsomal transformation to a toxic metabolite.

MeSH terms

  • Adult
  • Antipyrine / blood
  • Drug Interactions
  • Enzyme Induction / drug effects*
  • Female
  • Half-Life
  • Humans
  • Isoniazid / toxicity
  • Liver / metabolism
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • Middle Aged
  • Oxidation-Reduction
  • Oxidoreductases / metabolism
  • Rifampin / administration & dosage*
  • Rifampin / adverse effects

Substances

  • Oxidoreductases
  • Antipyrine
  • Isoniazid
  • Rifampin