摘要
Abstract
Objective To study the bioequivalence of efavirenz,lamivudine and tenofovir disoproxil fumarate tablets(Ⅰ)from two different manufacturers in healthy Chinese participants under fasting conditions.Methods A randomized,single-center,open-label,single-dose,two-sequence,two-period,two-way crossover design.Forty-two eligible healthy subjects were enrolled.In each period,subjects received a single oral dose of the test or reference formulation of efavirenz lamivudine tenofovir tablets(specification:each tablet contains 0.4 g efavirenz,0.3 g lamivudine and 0.3 g tenofovir disoproxil fumarate)under fasting conditions.The plasma concentrations of efavirenz,lamivudine and tenofovir was performed using a validated liquid chromatography-tandem mass spectrometry(LC-MS/MS)method that had been fully validated.Pharmacokinetic parameters were calculated and the bioequivalence and safety of the two efavirenz lamivudine tenofovir tablets were evaluated.Results For efavirenz,the key pharmacokinetic parametersderived from the test and reference formulations were as follows:Cmax were(1 710.25±430.44)and(1 851.26±505.57)ng·mL-1,AUC0-72h were(37571.38±8 747.34)and(39 391.65±8 746.77)ng·mL-1·h,tmax were[3.23±1.13(1.00,3.17,5.00)]and[3.12±1.30(1.25,3.00,6.03)]h,and t1/2 were(77.08±61.79)and(71.11±39.45)h,respectively.For lamivudine:Cmax were(2 397.22±689.34)and(2 388.23±618.71)ng·mL-1,AUC0-t were(12 134.48±2526.28)and(12 324.11±2 891.50)ng·mL-1·h,tmax were[1.97±0.70(0.67,1.88,4.00)]and[2.04±0.90(0.67,2.00,4.51)]h,and t1/2 were(11.07±11.10)and(11.46±11.90)h,respectively.For tenofovir:Cmax were(287.40±86.07)and(304.71±91.49)ng·mL-1,AUC0-t were(2 516.91±583.47)and(2 507.40±573.45)ng·mL-1·h,tmax were[1.40±0.74(0.50,1.13,3.00)]and[1.39±0.84(0.33,1.25,4.00)]h,and t1/2 were(22.95±4.26)and(21.88±2.99)h,respectively.Under fasting conditions,the 90％confidence intervals of the main PK parameters of the test and reference formulations were all within 80.00％to 125.00％.Conclusion The test and reference formulations are bioequivalent under fasting conditions.关键词
依非韦伦/拉米夫定/富马酸替诺福韦二吡呋酯/生物等效性/药动学/液相色谱-串联质谱法Key words
efavirenz/lamivudine/tenofovir disoproxil fumarate/bioequivalence/pharmacokinetics/LC-MS/MS分类
医药卫生
