关键词: 复方合剂, 利福平, 药代动力学, 生物利用度, 质谱分析法

Abstract:  Objective To study the pharmacokinetics and relative bioavailability and to assess the bioequivalence of compound rifampicin in two kinds of fixed-dose combination (FDC) formulations containing four anti-tuberculosis agents for ensuring its quality of FDC formulations for rational drug use.  Methods The randomized, crossover study was conducted in 18 healthy male volunteers for each FDC formulation (FDC1 for study1 and FDC2 for study2). Totally, 36 individuals were enrolled in these 2 studies. There were 2 groups for each study, every 9 volunteers for each group. Using FDC formulation for tested preparation and separated formulation (rifampicin capsules) as reference preparation, a single oral dose of two preparations (reference preparation and FDC) was given to 2 groups’ volunteers respectively. The rifampicin concentrations in plasma of volunteers were determined by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated by DAS 3.1.5 software and the bioequivalence of each FDC formulation was evaluated. Results The major pharmacokinetics parameters of compound rifampicin of two FDC formulations were showed respectively. For FDC1 and FDC2, C_max were (11.4±3.4)mg·L^-1 and (12.2±3.8)mg·L^-1, T_1/2 were (3.7±1.2)h and (3.6±1.3)h, AUC_(0-t) were (91.4±30.8)mg·L^-1·h^-1 and (92.1±25.3)mg·L^-1·h^-1, AUC_(0-∞) were (93.3±31.3)mg·L^-1·h^-1 and (94.1±26.5)mg·L^-1·h^-1. The relative bioavailability of AUC _(0-t) was 94.7%(CI=89.5%－100.2%), 91.4%(CI=81.4%－95.6%), respectively. Conclusion The pharmacokinetics parameters shows that these two FDC formulations are both bioequivalent for rifampicin to the reference preparation. There is no significant difference for C_max, T_max between these two kinds of FDC formulations and the reference preparation.

Key words: Drug combinations, Rifampicin, Pharmacokinetics, Biological availability, Mass spectrometry