硫唑嘌呤片在健康人体的生物等效性

Bioequivalence of azathioprine tablets in healthy volunteers

目的研究硫唑嘌呤片(免疫抑制剂)在健康人体的相对生物利用度并评价其生物等效性。方法20名健康志愿者自身交叉、单剂量口服硫唑嘌呤受试和参比制剂各100 mg后,用反相高效液相色谱法测定血浆中其代谢物6-巯基嘌呤浓度。应用DAS软件计算药代动力学参数和相对生物利用度。结果6-巯基嘌呤受试制剂和参比制剂的平均药物浓度-时间曲线均符合一室模型,主要药代动力学参数:t1/2分别为(1.30±0.25),(1.30±0.34)h;tmax分别为(1.25±0.16),(1.24±0.21)h;Cmax分别为(48.44±17.09),(52.32±24.37)μg.L-1;AUC0-t分别为(89.49±19.25),(91.90±25.31)μg.h.L-1;AUC0-∞分别为(96.11±19.74),(98.36±24.66)μg.h.L-1。与参比制剂比较,受试制剂的相对生物利用度F0-t为(99.62±15.29)%,F0-∞为(99.39±13.59)%。结论2种硫唑嘌呤制剂具有生物等效性。

Objective To evaluate the relative bioavailabifity and bioequivalence of azathioprine tablets in healthy volunteers. Methods A single oral dose of 100 mg azathioprine test and reference tablets were given to 20 male healthy volunteers in a randomized crossover study. Plasma metabolite 6 - mercaptopurine of azathioprine was determined by RP- HPLC. The pharmacokinetic parameters and relative bioavailability were calculated with DAS program to evaluate the bioequivalence of the two preparations. Results The concentration -time curves were fitted to a one -compartment open model. The main pharmacokinetic parameters of azathioprine test and reference tablets were as follows ： t1/2were （ 1.30 ±0.25） and （1.30 ±0. 34） h; tmax were （1.25 ±0. 16） and （1.24± 0.21） h; Cmax were （48.44±17.09） and （52.32±24.37） μg· L^-1 ; AUC0-1 were （89.49 ± 19.25） and （91.90 ±25.31） μg· h · L^-1 AUC0-∞ were （96. 11 ±19.74） and （98.36±24.66）μg· h · L^-1, respectively. The relative bioavailability of F0-1 and F0-∞ were （99.62 ± 15.29） % and （99.39 ± 13.59） % , respectively. Conclusion The two azathiprine preparations are bioequivalent.