PHARMACOKINETICS OF RIFAPENTINE IN PATIENTS WITH VARYING DEGREES OF HEPATIC-DYSFUNCTION

In this open-label investigation, the pharmacokinetics of rifapentine and its active metabolite, 25-desacetyl-rifapentine, were characterize d in patients with varying degrees of hepatic dysfunction. Eight patie nts with mild-to-moderate chronic, stable hepatic dysfunction and seve n patients with moderate-to-severe hepatic dysfunction received single oral 600-mg doses of rifapentine. Maximum plasma concentration of rif apentine was lower, time to maximum plasma concentration (t(max)) was greater, and elimination half-life (t(1/2)) was longer in the patients with moderate-to-severe hepatic dysfunction than in those with mild-t o-moderate dysfunction. However, mean area under the concentration-tim e curve extrapolated to infinity (AUC(0-infinity)) for the two groups was similar. AUC(0-infinity) values in patients with hepatic dysfuncti on were 19% to 25% higher than values previously reported for healthy volunteers. The 25-desacetyl metabolite appeared in plasma slowly afte r th e single oral dose of rifapentine. Similar to findings for the pa rent drug, comparable plasma exposures of 25-desacetyl-rifapentine bas ed on AUC(0-infinity)were found in the two groups of patients with mil d-to-moderate and moderate-to-severe hepatic dysfunction. Rifapentine was well tolerated in this patient population, irrespective of the eti ology or severity of hepatic dysfunction. These safety and pharmacokin etic results suggest that no dosage adjustments for rifapentine are ne eded in patients with hepatic impairment. Journal of Clinical Pharmaco logy 1998;38:517-524 (C) 1998 The American College of Clinical Pharmac ology.