长期口服复方左旋炔诺孕酮长效避孕片的临床药代动力学及体内蓄积  

Clinical pharmacokinetic study on levonorgestrel and possible accumulation after long-term treatment of the monthly combined oral contraceptive

作　　者：周晓飞[1] 邵庆翔[1] 韩学军[2] 翁梨驹[2] 经小萍[2] 桑国卫[1] 

机构地区：[1]浙江省医学科学院,杭州310013 [2]北京朝阳医院

出　　处：《中国临床药理学与治疗学杂志》1998年第2期81-84,共4页

摘　　要：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?Aim With comparison of pharmacokinetic profiles of levonorgestrel after single and multiple administration of the combined oral contraceptive, this study would provide pharmacokinetic data for safety evaluation on proloned treatment of this monthly long_acting oral contraceptive. Methods Nine healthy fertile women received the monthly combined oral contraceptive (containing LNG 6 mg and quinestrol 3 mg) for up to 1 year. Blood samples were collected immediately prior to drug intake and at consecutive time points after oral administration for determination of serum LNG by RIA. Intraindividual comparison was applied in this longitudinal study. Results Serum LNG concentration_time curve showed an open two compartment model after single dose administration, with 2.86±1.60 hours for αT1/2 and 1.52±0.35 days for βT1/2. C max of LNG was observed after 2.56±1.13 h in the 1st treatment cycle. Mean Cmax was 141.36±70.20 nmol/L with significant interindividual variation. C max in 12 th treatment cycle reached to 314.83±128.55 nmol/L,which was much higher than that in the 1st cycle. AUC 0～28 were 182.42±135.85 and 533.96±319.31 nmol/L·d-1,respectively, also showing statistically significant difference. There was no meaningful difference on T max after single and multiple dosing. The mean value of βT1/2 in the 12th dosing was 1.67±0.48 days, which showed no marked changes, suggesting that multiple dosing did not influence the velocity of drug metabolism. Cd21 declined below 100 pg/ml. Conclusion There was no obvious accumulation of LNG after repeated dosing of this monthly long_acting combined oral contraceptive.

关 键 词：复方左旋炔诺孕酮 长效避孕片 临床药代动力学 体内蓄积 

分 类 号：R979.21[医药卫生—药品] R969.1[医药卫生—药学]