ATYPICAL INDUCTIVE PROPERTIES OF RIFAMPICIN

Hepatic and microsomal parameters, metabolism of cytochrome P-450-dependent substrates and spectral properties of cytochrome P-450 have been used in mice in order to classify rifampicin as an inducer by comparing it to phenobarbitone and 3-methylcholanthrene. Rifampicin significantly enhanced relative liver weight, cytochrome P-450 content, microsomal protein, weight of the 100,000 g pellet and shortened the zoxazolamine paralysis time. Compared on the basis of microsomal protein, of five substrate reactions only the ethylmorphine demethylation was enhanced; ethoxycoumarin deethylation and biphenyl 1-2-hydroxylation were unaltered; ethoxyresorufin de-ethylation and biphenyl-4-hydroxylation were decreased. The CO-cytochrome P-450 absorption maximum showed a blue shift of about 0.5 nm after only 1 day of rifampicin pretreatment, while there was no significant blue shift after 1 day of 3-methylcholanthrene pretreatment. Rifampicin has been shown to be an inducer in NMRI mice. Although resembling phenobarbitone it seems, however, to be a similarly atypical inducer as it is in man. © 1979.