复方左炔诺孕酮片在健康人体中的药动学及生物等效性研究

Pharmacokinetics and Bioequivalence of Compound Levonorgestrel Tablets in Healthy Subjects

目的:比较两种复方左炔诺孕酮片的人体生物等效性。方法:20例健康受试者随机交叉单剂量口服复方左炔诺孕酮片[含左炔诺孕酮(LNG)0.15 mg,炔雌醇(EE)0.03 mg]受试制剂或参比制剂1片。采用放射免疫法测定血浆中LNG和EE的浓度,并计算药动学参数,考察生物等效性。结果:LNG受试制剂与参比制剂的主要药动学参数分别为:tmax(1.40±0.13)、(1.45±0.50)h,cmax(11.35±0.71)、(11.18±0.75)nmol/L,t1/2(15.85±0.90)、(15.53±1.18)h,AUC0-72 h(102.50±16.00)、(104.27±18.19)nmol·h/L,人体相对生物利用度为(101.1±24.0)%;EE受试制剂与参比制剂的主要药动学参数分别为:tmax(1.400±0.170)、(1.425±0.118)h,cmax(0.088±0.005)、(0.087±0.004)ng/ml,t1/2(5.646±0.740)、(5.583±0.426)h,AUC0-72 h(0.445±0.021)、(0.444±0.019)ng·h/ml,人体相对生物利用度为(100.5±5.9)%。受试制剂的AUC0-72 h、cmax和tmax与参比制剂比较无显著差异。结论:LNG和EE的人体相对生物利用度在正常范围内,两种复方左炔诺孕酮片生物等效。

OBJECTIVE： To compare the bioequivalence between two kinds of Compound levonorgestrel tablets. METHODS： A single dose of test tablet or reference tablet of 0.15 mg Compound levonorgestrel （LNG） tablet and 0.03 mg ethinylestradiol （EE） were administered by randomized crossover way in 20 healthy volunteers. The plasma concentrations of LNG and EE were de- termined by radioimmunoassay. The pharmacokinetic parameters were calculated and bioequiavailability was investigated. RE- SULTS： Main pharmacokinetic parameters of test tablet vs. reference tablet of LNG were as follows： t1/2 were （1.40 ± 0.13）h vs. （1.45 ± 0.50）h; Cmax were （11.35 ± 0.71）nmol/L vs. （11.18 ± 0.75） nmol/L; t1/2 were （15.85 ± 0.90）h vs. （15.53 ± 1.18） h; AUC0-72 h were （102.50 ± 16.00） nmol-h/L vs. （104.27 ± 18.19） nmol-h/L. The relative bioavailability of LNG was （101.1 ± 24.0）%. Main pharmacokinetic parameters of test tablet vs. reference tablet of EE Were as follows ： tm,x were （ 1.400 _± 0.170）h vs. （ 1.425 ± 0.118）h; cmax were （0.088 ± 0.005）ng/ml vs. （0.087 ± 0.004）ng/ml; t1/2 were （5.646 ± 0.740）h vs. （5.583 ± 0.426）h; AUC0-72 h were （0.445 ± 0.021） ng-h/ml vs.（0.444 ± 0.019） ng.h/ml. The relative bioavailability of EE was （100.5 ± 5.9）%. There was no significant differ- ence in AUCo-72 h, Cmax and tmax of test tablet and reference tablet. CONCLUSIONS ： In normal range of relative bioavailability of LNG and EE, 2 kinds of Compound levonorgestrel tablet are bioequivalent.