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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.

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