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Gender can be an important variable in the absorption and disposition of some drugs. In this open-label study, 15 healthy, nonsmoking women received a single 600-mg oral dose of rifapentine. Plasma samples were obtained at frequent intervals for up to 72 hr after the dose to determine the pharmacokinetic (PK) parameters of rifapentine and its active metabolite, 25-desacetyl-rifapentine. Peak plasma rifapentine concentrations (Cmax) were observed 5.9 hr after ingestion of the single dose. The mean area under the rifapentine plasma concentration-time curve [AUC(0-->infinity)] was 325 micrograms.hr ml and the mean elimination half-life (t1/2) was 16.3 hr. Plasma concentrations for the 25-desacetyl metabolite peaked at 15.4 hr after the rifapentine dose and declined with a terminal half-life of 17.3 hr. These rifapentine and 25-desacetyl-rifapentine PK data in women were compared to data generated previously in healthy men. Striking similarities in the PK profiles of parent drug and metabolite were found in the two populations. Mean differences in rifapentine CL/F (12%) and t1/2 (2%) were small. The only adverse event reported in the female subjects was discoloration of the urine. Based on these PK and safety data, no dosage adjustments for rifapentine based on gender are recommended.

Isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) are the most important drugs for the treatment of tuberculosis (TB). The pharmacokinetics of all three drugs in the plasma of 24 healthy males were studied as part of a randomized cross-over phase I study of two dosage forms. Subjects ingested single doses of INH at 250 mg, RIF at 600 mg, and PZA at 1,500 mg. Plasma was collected for 36 h and was assayed by high-performance liquid chromatography. The data were analyzed by noncompartmental, iterative two-stage maximum a posteriori probability Bayesian (IT2B) and nonparametric expectation maximization (NPEM) population modeling methods. Fast and slow acetylators of INH had median peak concentrations in plasma (C[max]) of 2.44 and 3.64 microg/ml, respectively, both of which occurred at 1.0 h postdose (time of maximum concentrations of drugs in plasma [T(max)]), with median elimination half-lives (t1/2) of 1.2 and 3.3 h, respectively (by the NPEM method). RIF produced a median C(max) of 11.80 microg/ml, a T(max) of 1.0 h, and a t1/2 of 3.4 h. PZA produced a median C(max) of 28.80 microg/ml, a T(max) of 1.0 h, and a t1/2 of 10.0 h. The pharmacokinetic behaviors of INH, RIF, and PZA were well described by the three methods used. These models can serve as benchmarks for comparison with models for other populations, such as patients with TB or TB with AIDS.