左旋18—甲基炔诺酮事后药的药物动力学及药效学研究

本研究为6例健康妇女,在月经周期排卵前后,口服左旋18-甲基炔诺酮(简称18-甲)0.75mg/天,连续七天的药物动力学和药效学。服药期间,每日在服药前取血,此外在第一和第七天服药后1,2,4,8,12和24小时取前臂静脉血,放射免疫法测定血中18-甲水平。药—时曲线表明所有受试者均为开放二室模型,药时方程为C(t)=Ae~(-αt)+Be~(-βt)-(A+B)e~(-kat)。第一天服药后药物动力学参数:达峰时间T_(max)3.74±1.06h,峰值C_(max)=8.91±2.25ng/ml,消除半寿期t_(1/2)β=11.98±2.99h,K_a=0.476±0.1202h,表观分布容积V_d=102.8±35.81L,体内总廊清率Cl=6.34±2.37L/h,血药浓度—时间曲线下面积Auc=136.91±50.58ng/ml/h;第七天药物动力学参数:T_(max)=3.46±1.12h,C_(max)=6.92±2.39ng/ml,t_(1/2)β=14.45±4.55h,K_a=0.4584±0.1640h,V_d=147.81±76.01L,Cl=6.95±4.21L/h,Auc=134.25±56.29ng/ml/h。比较服药第一天和第七天的药物动力学参数经(?)t-test 计算,两者之间无统计学差异。服药期间,每日血标本用RIA法测定雌二醇E_2,孕酮P,促黄体生长激素LH,促卵泡激素FSH,和促泌乳激素PRL。结果发现血内FSH 水平明显偏低,6例中4例LH 峰偏低或消失;有两例孕酮峰消失;E_2及PRL 的变化较小,其值在正常范围内。

A STUDY ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF LEVONORGESTREL AS POSTCOITAL CONTRACEPTIVE AGENT

Pharmacokinetics and pharmacodynamics of levonorgestrel were studied in six healthfemale volunteers.A daily oral dose of 0.75 mg of levonorgestrel was given for seven daysduring periovlatory phase of the menstrual cycle.Blood samples were taken daily at 8:00am for measurement of serum levonorgestrel by RIA and collected 1,2,4,8,12 and 48 hrsafter administration of the drug on day 1 and 7.The curves of serum concentration versustime showed that a two compartment open model could be used in all subjects with an equationC(t)=Ae~(αt)-Be~(βt)-(A+B)e~(-K) a~t and the following pharmacokinetic parameters(mean value)of first day T_(max)=3.74±1.06h,C_(max)=8.91±2.25ng/ml t_(1/2)β=11.98±2.99h,k_a=0.47610.1202h,Vd=102.86±35.81L,Cl=6.34±2.37L/h,AUC_(0-∞)=136.91±50.58ng/ml/h.The parameters of day 7 were:T_(max)=3.46±1.12h,C_(max)=6.92±2.39ng/ml,t_(1/2)β=14.45±4.55h,k_a=0.4584±0.1640h,Vd=147.81±76.01L,Cl=6.95±4.21L/h,AUC_(0-∞)=134.25±56.29 ng/ml/h.No significant difference of corresponding pharmacokineticparameters was found between day 1 and day 7 treatment.Serum E_2,P,FSH,LH andPRL were measured daily during treatment by RIA.The results show that serum levelsof PRL were in normal range,but FSH and LH levels were rather low.The peak of Pdisappeared in 2 out of 6 cases.