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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。
OBJECTIVE: To compare human pharmacokinetics and relative bioavailability of levonorgestrel orally disintegrating tablets with those of oral tablets. Methods: Twenty healthy female volunteers were randomly assigned to double-crossover single-dose levonorgestrel orally disintegrating tablets and commercial oral tablets at a dose of 0.75 mg. Venous blood samples were taken at different time points before taking the drug and within 72 hours after taking the drug. , And the cleaning period was 2 weeks. The concentration of levonorgestrel in serum was determined by radioimmuno-assay (RIA) method. The pharmacokinetics and relative value of oral tablets and oral tablets were calculated by SAS software bioavailability. Results: The lowest limit of detection of levonorgestrel by RIA was 10 pg / ml, levonorgestrel at low, medium and high concentrations (300 pg / ml, 2 000 pg / ml and 6 000 pg / ml) The intra-day precision of the standard quality control serum was 12.4%, 9.3% and 3.1%, respectively. The intra-day precision was 4.3%, 11.7% and 5.7%, respectively (n = 5). The main pharmacokinetic parameters of the orally disintegrating tablet and the commercially available oral tablet were: tmax 1.6 ± 0.2 h, tmax 1.7 ± 0.3 h, Cmax 6.2 ± 0.8 ng / ml, Cmax 6.5 ± 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. The 90% confidence intervals of AUC0 ~ 72 h, AUC0-inf and Cmax of oral tablets were 87.72% ~ 101.87%, 89.01% ~ 103.73% and 89.80% ~ 101.75% of the corresponding oral tablets. Oral disintegrating tablets tmax compared with the commercially available oral tablets no significant difference (P> 0.05). The relative bioavailability of the orally disintegrating tablet was 96.1 ± 18.3%. Conclusion: The established analytical method is accurate and sensitive, and can be used for the determination of levonorgestrel plasma concentration. The bioavailability of levonorgestrel orally disintegrating tablets is not significantly different from that of the commercially available oral tablets. The two preparations have biological Validity.