利福布汀与依非韦伦在大鼠体内药动学的相互作用研究

Interaction of Rifabutin and Efavirenz on Pharmacokinetics in Rats

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。

OBJECTIVE： To study the effects to each other of rifabutin （RBT） and efavirenz （EFV） on pharmacokinetics in rats. METHODS： Rats were randomized into EFV group （54 mg. kg-l）, RBT group （40.5 mg. kg-1） and drug combination group with 6 rats in each group. After intragastric administration, the blood concentrations of drugs were determined by LC-MS/MS 0, 0.25,0.5,1, 2, 3, 4, 6, 9, 12, 24, 48, 72 h after administration, and pharmacokinetic parameters were calculated. RESULTS： When they were used alone, the pharmacokinetic parameters of EFV vs. RBT were as follows： Cmax： （4.36 ± 1.23）, （5.62 ± 2.33） mg.L-1; AUC ：（27.37±8.10）, （117.00±50.45）mg.h.L-1; CL_z/F：（2.15±0.77）, （0.36±0.15）L.h -1.kg-1; V）z/F：（8.33± 2.49）, （12.06 ± 7.64） L.kg-1. When they were combined, the pharmacokinetic parameters of EFV vs. RBT were as follows： Cmax： （1.68±0.82）, （3.05± 1.66） mg.L-1; AUC ：（13.13±9.95）, （89.60±55.75） mg-h.L-1; CL_z/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. Compared with other 2 groups, the Cmax and AUC_0-72 h of drug combina- tion group were significantly decreased, while CL_z/F and V_z/F were significantly increased （P〈0.05）. The pharmacokinetic parame- ters of RBT had no significant difference. CONCLUSION： Rifabutin can speed up the elimination of efavirenz in rats and reduce bioavailability of it.