Induction of hepatic microsomal enzymes after brief administration of rifampicin in man.
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.
D000328:Adult; D000983:Antipyrine / Q000097:blood; D004347:Drug Interactions; D004790:Enzyme Induction / Q000187:drug effects*; D005260:Female; D006207:Half-Life; D006801:Humans; D007538:Isoniazid / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D008875:Middle Aged; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism; D012293:Rifampin / Q000008:administration & dosage* / Q000009:adverse effects
D010088:Oxidoreductases; D000983:Antipyrine; D007538:Isoniazid; D012293:Rifampin