论文部分内容阅读
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。
This study was conducted in 6 healthy women who received oral 0.75 mg / day of 18-norgestrel (abbreviated 18-A) 0.75 mg / day before and after menstrual cycle ovulation for pharmacokinetics and pharmacodynamics for seven consecutive days. During the medication, blood was taken daily before taking the medication, and forearm venous blood was taken at 1, 2, 4, 8, 12 and 24 hours after the first and seventh days of medication, and 18-A levels in the blood were measured by radioimmunoassay. Drug-time curve showed that all subjects were open two-compartment model, the drug time equation is C (t) = Ae ~ (-αt) + Be ~ (-βt) - (A + B) e ~ (-kat) . The first day after taking the drug pharmacokinetic parameters: peak time T_ (max) 3.74 ± 1.06h, the peak value of C_ (max) = 8.91 ± 2.25ng / ml, eliminate half life t_ (1/2) β = 11.98 ± 2.99 h, K_a = 0.476 ± 0.1202h, the apparent volume of distribution V_d = 102.8 ± 35.81L, total body clearance rate of the body Cl = 6.34 ± 2.37L / h, the area under the plasma concentration-time curve Auc = 136.91 ± 50.58ng / ml / h; On the seventh day, the pharmacokinetic parameters were as follows: T max = 3.46 ± 1.12 h, C max = 6.92 ± 2.39 ng / ml, t 1/2 (1/2) β = 14.45 ± 4.55 h, K a = 0.4584 ± 0.1640 h, V_d = 147.81 ± 76.01 L, Cl = 6.95 ± 4.21 L / h, Auc = 134.25 ± 56.29 ng / ml / h. Pharmacokinetic parameters of the first day and the seventh day of comparison were calculated by (?) T-test, there was no significant difference between the two. During the medication, daily blood samples were measured by RIA estradiol E_2, progesterone P, luteinizing hormone LH, follicle stimulating hormone FSH, and prolactin hormone PRL. The results showed that blood FSH levels were significantly lower, 6 cases of 4 cases of LH peak low or disappear; two cases of progesterone peak disappeared; E_2 and PRL changes in small, its value within the normal range.