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目的研究左炔诺孕酮分散片在人体内药动学和生物等效性。方法采用双周期交叉试验设计,20名健康女性受试者随机交叉单剂量口服1.5mg左炔诺孕酮试验制剂和参比制剂,以高效液相色谱-质谱联用法测定人血浆中左炔诺孕酮经-时血药浓度,用DASVer2.0软件计算药动学参数,评价两制剂的生物等效性。结果左炔诺孕酮试验制剂和参比制剂的主要药动学参数Cmax分别为(29.28±6.15)ng·mL-1和(30.63±6.44)ng·mL-1;Tmax分别为(1.71±0.24)h和(1.75±0.23)h;t1/2分别为(17.56±6.07)h和(17.77±6.22)h;CL/F分别为(5.00±1.99)L·h-1和(4.76±1.83)L·h-1;AUC0→t分别为(316.56±94.25)ng·h·mL-1和(334.32±109.64)ng·h·mL-1,AUC0→∞分别为(332.53±93.58)ng·h·mL-1和(351.35±108.11)ng·h·mL-1;试验制剂的AUC0-t,AUC0-∞,Cmax的90%置信区间分别为参比制剂相应参数的89.1%～102.1%、89.0%～101.5%和91.8%～100.0%。以AUC0→t计算试验制剂中左炔诺孕酮对参比制剂的相对生物利用度F为(96.85±18.23)%。结论经方差分析及双单侧t检验结果显示,试验制剂和参比制剂具有生物等效性。
Objective To study the pharmacokinetics and bioequivalence of levonorgestrel dispersible tablets in human. Methods A two-cycle crossover design was used. Twenty healthy female subjects were randomized to receive 1.5 mg of levonorgestrel oral solution and reference formulation at randomized crossover doses. The levels of levonorgestrel in human plasma were determined by high performance liquid chromatography-mass spectrometry Progesterone by - time plasma concentration, using pharmacokinetic parameters DASVer2.0 software to evaluate the bioequivalence of the two preparations. Results The main pharmacokinetic parameters Cmax of Levonorgestrel test preparations and reference preparations were (29.28 ± 6.15) ng · mL-1 and (30.63 ± 6.44) ng · mL-1, respectively; Tmax were (1.71 ± 0.24 (17.56 ± 6.07) h and (17.77 ± 6.22) h respectively; CL / F were (5.00 ± 1.99) L · h-1 and (4.76 ± 1.83) h respectively L · h-1; AUC0 → t were (316.56 ± 94.25) ng · h · mL-1 and (334.32 ± 109.64) ng · h · mL-1, respectively; AUC0 → ∞ were (332.53 ± 93.58) ng · h · ML-1 and (351.35 ± 108.11) ng · h · mL-1, respectively. The 90% confidence intervals of AUC0-t, AUC0-∞ and Cmax of the test preparation were 89.1% ~ 102.1% and 89.0 % ~ 101.5% and 91.8% ~ 100.0%. The relative bioavailability of levonorgestrel to the reference formulation, F, was calculated as (96.85 ± 18.23)% with AUC0 → t. Conclusion The analysis of variance and double unilateral t-test showed that the test preparation and the reference preparation were bioequivalent.