A C Keung1, M G Eller, S J Weir. 1. North America Pharmacokinetics, Hoechst Marion Roussel, Inc., Kansas City, Missouri 64134, USA.
Abstract
PURPOSE: This study was undertaken to characterize the pharmacokinetic profiles of rifapentine and its active metabolite, 25-desacetlyl rifapentine, in elderly men. METHODS: Fourteen healthy, nonsmoking male volunteers between the ages of 65 and 82 years received a single oral 600 mg dose of rifapentine. Plasma samples were collected at frequent intervals for up to 72 hours postdose. The control group consisted of 20 healthy, young (18-45 years) males volunteers from a previous, single-dose (600 mg) rifapentine pharmacokinetic study. RESULTS: Plasma rifapentine concentrations above the minimum inhibitory concentration for M. tuberculosis were observed at 2 hours after dosing. Disposition of rifapentine was monophasic with a mean terminal half-life of 19.6 hours. The peak plasma concentration of 25 desacetyl-rifapentine was found 21.7 hours, on average, after the rifapentine dose; the mean 25-desacetyl-rifapentine t1/2 was 22.9 hours. Compared to the younger subjects, apparent oral clearance of rifapentine (24%) was lower in the elderly male (p < 0.05), and Cmax (28%) was higher. The only adverse event reported in both the older and younger subjects in these single-dose studies was discoloration of the urine. CONCLUSIONS: Because the aged-related changes in the pharmacokinetic profile of rifapentine observed in this study were modest and unlikely to be associated with toxicity, no dosage adjustments for this antibiotic are recommended in elderly patients.
PURPOSE: This study was undertaken to characterize the pharmacokinetic profiles of rifapentine and its active metabolite, 25-desacetlyl rifapentine, in elderly men. METHODS: Fourteen healthy, nonsmoking male volunteers between the ages of 65 and 82 years received a single oral 600 mg dose of rifapentine. Plasma samples were collected at frequent intervals for up to 72 hours postdose. The control group consisted of 20 healthy, young (18-45 years) males volunteers from a previous, single-dose (600 mg) rifapentine pharmacokinetic study. RESULTS: Plasma rifapentine concentrations above the minimum inhibitory concentration for M. tuberculosis were observed at 2 hours after dosing. Disposition of rifapentine was monophasic with a mean terminal half-life of 19.6 hours. The peak plasma concentration of 25 desacetyl-rifapentine was found 21.7 hours, on average, after the rifapentine dose; the mean 25-desacetyl-rifapentine t1/2 was 22.9 hours. Compared to the younger subjects, apparent oral clearance of rifapentine (24%) was lower in the elderly male (p < 0.05), and Cmax (28%) was higher. The only adverse event reported in both the older and younger subjects in these single-dose studies was discoloration of the urine. CONCLUSIONS: Because the aged-related changes in the pharmacokinetic profile of rifapentine observed in this study were modest and unlikely to be associated with toxicity, no dosage adjustments for this antibiotic are recommended in elderly patients.
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