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目的:研究利福布汀(RBT)与依非韦伦(EFV)在大鼠体内药动学的相互影响。方法:将大鼠随机分为EFV单用组(54mg·kg-1)、RBT单用组(40.5mg·kg-1)及其联用组,每组6只,灌胃给药后,液质联用法检测给药后0、0.25、0.5、1、2、3、4、6、9、12、24、48、72h的血药浓度,计算药动学参数。结果:单用时,EFV、RBT的药动学参数分别为:cmax:(4.36±1.23)、(5.62±2.33)mg·L-1,AUC0～72h:(27.37±8.10)、(117.00±50.45)mg·h·L-1,CLZ/F:(2.15±0.77)、(0.36±0.15)L·h-1·kg-1,VZ/F:(8.33±2.49)、(12.06±7.64)L·kg-1;联用组二者的药动学参数分别为cmax:(1.68±0.82)、(3.05±1.66)mg·L-1,AUC0～72h:(13.13±9.95)、(89.60±55.75)mg·h·L-1,CLZ/F:(5.12±2.17)、(0.54±0.24)L·h-1·kg-1,VZ/F:(23.53±11.43)、(13.06±4.75)L·kg-1。与单用时比较,联用组EFV的cmax、AUC0～72h显著减小,CLZ/F、VZ/F显著增加(P<0.05),而RBT药动学各参数未见显著变化。结论:RBT能加快大鼠体内EFV的消除,降低其生物利用度。
AIM: To investigate the pharmacokinetics of rifabutin (RBT) and efavirenz (EFV) in rats. Methods: The rats were randomly divided into EFV single-use group (54mg · kg-1), RBT single-use group (40.5mg · kg-1) and its combination group, The qualitative and quantitative methods were used to detect the plasma concentrations at 0, 0.25, 0.5, 1, 2, 3, 4, 6, 9, 12, 24, 48 and 72 h after administration, and the pharmacokinetic parameters were calculated. Results: The pharmacokinetic parameters of EFV and RBT were (4.36 ± 1.23), (5.62 ± 2.33) mg · L-1, AUC0 ~ 72h: (27.37 ± 8.10) and (117.00 ± 50.45) (8.33 ± 2.49), (12.06 ± 7.64) L · min-1 · h · L-1, CLZ / F: kg-1. The pharmacokinetic parameters of the combined group were cmax: (1.68 ± 0.82), (3.05 ± 1.66) mg · L-1, AUC0 ~ 72h: (13.13 ± 9.95), (89.60 ± 55.75) (5.12 ± 2.17), (0.54 ± 0.24) L · h-1 · kg-1, VZ / F: (23.53 ± 11.43), (13.06 ± 4.75) L · kg-1. Compared with the single use, the cmax, AUC0 ~ 72h, the CLZ / F, VZ / F of EFV in combination group were significantly increased (P <0.05), while the parameters of RBT pharmacokinetics did not change significantly. Conclusion: RBT can accelerate the elimination of EFV in rats and reduce its bioavailability.