【摘要】 目的　研究单剂量口服来氟米特 (leflunomide,Lef)在中国健康志愿者的药动学。方法　 1 8名健康志愿者随机分为 3组 ,分别单剂量 poLef(2 0 ,40 ,60mg) ;高效液相色谱法检测血清中Lef活性代谢物A771 72 6 浓度 ,以 3P97药动学程序计算药动学参数。结果　A771 72 6 的血药浓度 时间曲线符合一级吸收的一房室模型。 poLef 2 0 ,40 ,60mg的主要药动学参数为 :t1 / 2Ka:(0 .0 9± 0 .1 2 ) ,(0 .1± 0 .3)和 (0 .0 5± 0 .0 3)d ;t1 / 2Ke:(8.8± 0 .8) ,(7.1± 1 .0 )和 (1 0 .5± 1 .1 )d ;tmax:(0 .6± 0 .5) ,(0 .55±0 .1 6)和 (0 .38± 0 .2 9)d ;cmax:(2 .0± 0 .5) ,(5 .2 0± 0 .1 7)和 (6 .7± 1 .5)mg·L- 1 ;AUC0～ 2 8d:(2 7± 6) ,(56± 8)和 (1 0 6± 30 )mg·d·L- 1 。结论　本品口服吸收快 ,消除慢。单剂量 poLef(2 0 ,40 ,60mg) ,其活性代谢物A771 72 6 的血药浓度 时间曲线符合一级吸收的一房室模型。更多还原

【Abstract】 OBJECTIVE To study the pharmacokinetics of leflu no mide in Chinese healthy volunteers.METHODS A single oral dos es of leflunomide(20,40,60 mg) were performed in 18 (12 males and 6 females) Chi nese healthy volunteers respectively in a randomized crossover way.The concentra tions of A 771726 ,leflunomide’s active metabolite,in serum were determined by HPLC.Data were analyzed by using a 3P97 program on a Legend computer.RESULTS The serum concentration-time curves of A 771726 follow ing single oral administration of leflunomide conformed to one compartment model of the first order absorption.Leflunomide was absorbed rapidly with t 1/ 2 Ka of between 0.048 and 0.093 day.The major pharmacokinetic parameters of A 771726 in 20,40,60 mg groups were t 1/2Ka :(0.09±0.12),(0.1±0.3) and (0.05±0.03) d;t 1/2Ke :(8.8±0.8),(7.1±1.0) and (10.5±1.1) d; t max :(0.6±0.5),(0.55±0.16) and (0.38±0.29) d;c max :(2.0± 0.5),(5.20±0.17) and (6.7±1.5) mg·L -1 ; AUC 0～28d :(27±6),(5 6±8) and (106±30) mg·d·L -1 ,respectively.CONCLUSION The absorption of leflunomide was rapid,and its elimination was slow after ora l administration.The pharmacokinetic results showed that it exhibited first orde r kinetic characteristics.更多还原