左炔诺孕酮口崩片的人体药代动力学及相对生物利用度研究

目的:比较左炔诺孕酮口崩片和市售口服片的人体药代动力学及相对生物利用度。方法:20名健康女性志愿者随机双交叉单剂量服用左炔诺孕酮口崩片和市售口服片,剂量均为0.75 mg,分别于服药前和服药后72 h内不同时间点抽取静脉血,清洗期为2周,以放射免疫分析(radioimmuno-assay,RIA)法测定血清中左炔诺孕酮的浓度,并利用SAS软件计算口崩片与市售口服片的药代动力学和相对生物利用度。结果:采用RIA测定左炔诺孕酮的最低检测限为10 pg/ml,低、中、高(300 pg/ml、2 000 pg/ml、6 000 pg/ml)3种浓度左炔诺孕酮标准质控血清的日内精密度分别为12.4%、9.3%、3.1%(n=5),日间精密度分别为4.3%、11.7%、5.7%(n=5)。口崩片和市售口服片的主要药代动力学参数分别为:tmax1.6±0.2 h、tmax1.7±0.3 h;Cmax6.2±0.8 ng/ml、Cmax6.5±1.0 ng/ml;AUC0～72 h 85.5±24.4 h.ng/ml、AUC0～72 h 90.8±27.1 h.ng/ml;AUC0-inf96.8±27.9 h.ng/ml、AUC0-inf 101.2±30.8 h.ng/ml;t1/2 25.3±3.5 h、t1/224.2±3.1 h。口崩片的AUC0～72 h、AUC0-inf和Cmax的90%置信区间分别为市售口服片相应参数的87.72%～101.87%、89.01%～103.73%和89.80%～101.75%。口崩片tmax与市售口服片相比无显著差异(P>0.05)。口崩片的相对生物利用度为96.1±18.3%。结论:建立的分析方法准确灵敏,可用于左炔诺孕酮血药浓度的测定;左炔诺孕酮口崩片与市售口服片的生物利用度无显著性差异,2种制剂具有生物等效性。

Study on Pharmacokinetic and Relative Bioavailability of Rapid Oral Disintegrating Tablet of Levonorgestrel

Objective: To compare the pharmacokinetics and relative bioavailability of rapid oral disinte- grating tablet and those of market available tablet of levonorgestrel(LNG). Methods: Twenty healthy female volunteers were given single oral dose of LNG rapid oral disintegrating tablet and market available tablet in a randomised crossover study. The dose was 0.75 mg. The blood samples were collected at different time points before and after taking the medication within 72 h. The plasma concentration was determined by radioimmunoassay (RIA) method. The pharmacokinetic parameters and relative bioavailability were calculated using SAS software. Results: The limit of detection was 10 pg/ml. The intra-day precision RSD of 3 different concentrations (300 pg/ml, 2 000 pg/ml, 6 000 pg/ml) of quality control plasma were 12.4%, 9.3%, 3.1%, respectively (n =5), and the inter-day precision RSD were 4.3%, 11.7%, 5.7%, respectively (n=5). The main pharmacokinetic parameters of rapid oral disintegrating tablet and market available tablet were as follows: tmax 1.6 ± 0.2 h and 1.7 ± 0.3 h; Cmax 6.2 ± 0.8 ng/ml and 6.5 ± 1.0 ng/ml; AUC0-72 h 85.5 ± 24.4 h·ng/ml and 90.8 ± 27.1 h·ng/ml; AUC0-inf 96.8 ± 27.9 h·ng/ml and 101.2 ± 30.8 h·ng/ml; t1/2 25.3 ± 3.5 h and 24.2 ± 3.1 h, respectively. The rapid oral disintegrating tablet AUC0-72 h, AUC0-inf and Cmax of the 90% confidence fell market available tablet 86.85%-98.02%, 98.12%-110.20% and 86.40%-98.12% range. Tmax test showed no significant difference between them (P>0.05). The relative bioavailability of rapid oral disintegrating tablet to market available tablet was 96.1 ± 18.3%. Conclusion: The assay was shown to be sensitive, accurate, and the results were reliable. The relative bioavailability had no significant difference between rapid oral disintegrating tablet and market available tablet. The two formulations are bioequivalent.