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Abstract

The effects of rifapentine (MDL 473) administration on hepatic mixed function oxidase activity in man have been investigated in six healthy volunteers. 2 Administration of rifapentine (600 mg 48 h7l) 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-' to 67.4 ± 5.6 ml min-'). Twelve days after stopping rifapentine administration, these values had largely returned to base-line. 3 24-Hour excretion of 6p-hydroxycortisol was significantly increased, by approximately threefold , following administration of rifapentine for 10 days. Again, 12 days after stopping drug administration, 6p-hydroxycortisol excretion had returned to pretreatment values. 4 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. 5 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.