Induction and autoinduction properties of rifamycin derivatives: a review of animal and human studies.

Animal studies have demonstrated that the mouse and rabbit are far more responsive to the inductive properties of rifamycin derivatives than the rat and guinea pig. The rat hepatic cytochrome P450 system seems to be resistant to the action of rifampicin unless very high doses are used. Mouse hepatic microsomal mixed-function oxidase activity is markedly increased by repeated dosing with rifampicin, whereas administration of rifabutin may be ineffective. In humans, both rifampicin and rifabutin are extensively metabolized and induce their own metabolism. The induced metabolic pathways remain essentially unknown. Under autoinduction conditions, the elimination half-life of rifampicin decreases, whereas that of rifabutin is not altered. Although the effects of repeated administration of rifampicin and rifabutin on the various forms of cytochrome P450 in humans have not been extensively examined, there is convincing evidence that the P4503A subfamily is induced by either drug, whereas the P4501A subfamily and P4502D6 do not appear to be affected by rifampicin. Limited reliable information is available concerning the induction of human glucuronyltransferase activities by rifampicin and rifabutin which, however, do not seem to influence zidovudine glucuronide formation in healthy subjects.