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 drugmetabolizing 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.