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目的比较中国妇女单剂及连续口服复方左旋炔诺孕酮长效避孕片后体内左旋炔诺酮(LNG)的药代动力学变化 ,为长期应用该长效避孕片的安全性提供依据。方法9例健康育龄妇女于月经第5天口服复方左旋炔诺孕酮长效片(左旋炔诺孕酮6mg+炔雌醚3mg) ,每月1片 ,连续服用1年。于第1和第12次给药前及给药后不同时间取血 ,放射免疫法测定血清LNG浓度 ,并采用自身对照比较单剂和长期给药后LNG的药代动力学特征。结果首次单剂给药后LNG药 -时曲线呈二室开放模型 ,分布半衰期(αT1/2)为2.86±1.60小时 ,消除半衰期(βT1/2)为1.52±0.35天。血清LNG于2.56±1.13小时达峰浓度 ;血药峰值水平(Cmax)存在明显的个体差异 ,平均为141.36±70.20nmol/L。服用第12片后LNG平均Cmax 为314.83±128.55nmol/L ,显示连续给药后血LNG峰浓度显著升高。第1和第12次用药后AUC0～∞分别为182.42±135.85nmol/L·d -1和601.60±320.99nmol/L·d -1,两者亦有显著的统计学差异。第12次服药后Tmax 为2.11±0.78小时 ,与单次给药相比无显著变化。第12次服药后LNG平均βT1/2 为1.67±0.48天 ,与单剂给药相比亦无统计学差异 ,表明多次给药后药物的代谢速率并未发生明显改变 ,且21天体内LNG血浓度已降至0.058±0.069nmol/L(<100pg/ml)。结论长期应用?
Objective To compare the pharmacokinetics of levonorgestrel (LNG) with Chinese single-dose or continuous oral levonorgestrel long-term contraceptive tablets in order to provide evidence for long-term use of this long-acting contraceptive tablet. Methods Nine healthy women of childbearing age were given oral levonorgestrel long-acting tablets (levonorgestrel 6 mg + ethinyl estradiol 3 mg) on the fifth day of menstruation for 1 year continuously for 1 year. Blood samples were collected before and after administration of the first and 12th administration, and serum levels of LNG were determined by radioimmunoassay. Pharmacokinetic characteristics of LNG after single administration and long-term administration were compared with self-control. Results The first time dose of LNG showed a two-compartment open model with a half-life (αT1 / 2) of 2.86 ± 1.60 hours and an elimination half-life (βT1 / 2) of 1.52 ± 0.35 days. Serum LNG peaked at 2.56 ± 1.13 hours; there was a significant individual difference in peak plasma level (Cmax), with an average of 141.36 ± 70.20 nmol / L. The average Cmax of LNG taken after the 12th tablet was 314.83 ± 128.55nmol / L, which showed that the peak LNG concentration of blood was significantly increased after continuous administration. The AUC0 ~ ∞ after the first and the 12th administration were 182.42 ± 135.85nmol / L · d -1 and 601.60 ± 320.99nmol / L · d -1, respectively. There was also a significant statistical difference between the two groups. The Tmax after the 12th dose was 2.11 ± 0.78 hours, with no significant change from the single dose. The average LNG βT1 / 2 after the 12th dose was 1.67 ± 0.48 days, no significant difference compared with the single dose administration, indicating that the metabolism rate of the drug did not change significantly after multiple administrations and the LNG Blood concentrations have dropped to 0.058 ± 0.069 nmol / L (<100 pg / ml). Conclusion long-term application?