Rifapentine pharmacokinetics in adolescents

Objective. Determination of rifapentine pharmacokinetics in healthy adolesc ent children. Design. Prospective Phase II clinical trial. Setting. Clinica l research center within a university children's hospital, Patients. Twelve subjects ranging in age fi om 12 to 15 years, male and female, Interventio ns. A, single oral dose of rifapentine was administered to healthy adolesce nt volunteers, 450 mg if <45 kg or 600 mg if greater than or similar to 45 kg,Blood was collected at serial intervals (0, 2, 3, 4, 5, 6, 8, 12, 18, 24 , 48 and 72 h postdose). Subjects were observed for adverse effects during the period of study. Measurements, High pressure liquid chromatography was used to measure the plasma concentration of rifapentine and 25-desacetyl ri fapentine in each blood sample, For each subject a plot of mean plasma conc entration vs. time data for rifapentine and its metabolite (i.e, 25-desacet yl rifapentine) were created. Subsequently model-independent methods were u sed to determine the pharmacokinetic profiles for each subject. Results. Al l subjects tolerated rifapentine without adverse effects. The 2-h postdose plasma concentrations of rifapentine (6.59 to 9.05 mu g/ml) and 25-desacety l rifapentine (0.57 to 2.84 mu g/ml) far exceeded the MIC of Mycobacterium tuberculosis to rifapentine (similar to 0.12 mu g/ml). The combination of a high C-max (rifapentine, 9.95 to 18.63 mu g/ml; 25-desacetyl rifapentine, 3.73 to 7.46 mu g/ml) and lengthy terminal elimination phase t(1/ 2) (rifap entine, 10 to 23 h; 25-desacetyl rifapentine, 14 to 35 h) resulted in poten tially effective plasma concentrations of both compounds that persisted for at least 48 h in most subjects. Conclusions. A web-tolerated oral rifapent ine dose produced rapid and sustained plasma drug concentrations in adolesc ents that should effectively treat infections caused by M. tuberculosis. Ri fapentine pharmacokinetics appears to be similar in adolescent and adult po pulations.