SINGLE-DOSE PHARMACOKINETICS OF RIFAPENTINE IN ELDERLY MEN

Purpose. This study was undertaken to characterize the pharmacokinetic profiles of rifapentine and its active metabolite, 25-desacetyl-rifap entine, in elderly men. Methods. Fourteen healthy, nonsmoking male vol unteers between the ages of 65 and 82 years received a single oral 600 mg dose of rifapentine. Plasma samples were collected at frequent int ervals for up to 72 hours postdose. The control group consisted of 20 healthy, young (18-45 years) male volunteers from a previous, single-d ose (600 mg) rifapentine pharmacokinetic study. Results. Plasma rifape ntine concentrations above the minimum inhibitory concentration for M. tuberculosis were observed at 2 hours after dosing. Disposition of ri fapentine was monophasic with a mean terminal half-life of 19.6 hours. The peak plasma concentration of 25-desacetyl-rifapentine was found 2 1.7 hours, on average, after the rifapentine dose; the mean 25-desacet yl-rifapentine t(1/2) was 22.9 hours. Compared to the younger subjects , apparent oral clearance of rifapentine (24%) was lower in the elderl y male (p < 0.05), and Cmax (28%) was higher. The only adverse event r eported in both the older and younger subjects in these single-dose st udies was discoloration of the urine. Conclusions, Because the age-rel ated changes in the pharmacokinetic profile of rifapentine observed in this study were modest and unlikely to be associated with toxicity, n o dosage adjustments for this antibiotic are recommended in elderly pa tients.