title: Induction of mixed function oxidase activity in man by rifapentine (MDL 473), a long-acting rifamycin derivative.
abstract: The effects of rifapentine (MDL 473) administration on hepatic mixed function oxidase activity in man have been investigated in six healthy volunteers. Administration of rifapentine (600 mg 48 h-1) for 10 days resulted in a significant reduction in antipyrine half-life (from 13.2 +/- 1.0 h to 7.7 +/- 0.4 h) and a corresponding increase in its total body clearance (from 41.8 +/- 5.5 ml min-1 to 67.4 +/- 5.6 ml min-1). Twelve days after stopping rifapentine administration, these values had largely returned to base-line. 24-Hour excretion of 6 beta-hydroxycortisol was significantly increased, by approximately three-fold, following administration of rifapentine for 10 days. Again, 12 days after stopping drug administration, 6 beta-hydroxycortisol excretion had returned to pretreatment values. Clearance of antipyrine to its three oxidative metabolites was increased by rifapentine administration, although the increase for 3-hydroxymethylantipyrine was not significant. The greatest increase (+140%) was observed for norantipyrine. Twelve days after the last dose of rifapentine, all values had returned to control levels. It is concluded that, like rifampicin, rifapentine is a potent inducer of mixed function oxidase activity in man and that the possibility of clinically significant drug interactions should be anticipated in the therapeutic use of this compound.
mesh_terms: D000328:Adult; D000983:Antipyrine / Q000378:metabolism; D001711:Biotransformation; D004790:Enzyme Induction / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D012293:Rifampin / Q000031:analogs & derivatives* / Q000494:pharmacology; D012463:Saliva / Q000378:metabolism; D013997:Time Factors
chemical_list: C001380:6 beta-hydroxycortisol; D006899:Mixed Function Oxygenases; D000983:Antipyrine; D012293:Rifampin; D006854:Hydrocortisone; C018421:rifapentine