口服左旋18—甲基炔诺酮的药代动力学

来源 :中国临床药理学杂志 | 被引量 : 0次 | 上传用户:aoyun2000
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10例健康育龄妇女,于月经第5天一次口服左旋“18-甲”6mg。在服药前及服药后不同时间取静脉血,放射免疫法测定血中“18-甲”水平。左旋“18-甲”血浓度的平均达峰时间为3.20±1.93(M±SD,下同)小时,血药峰值显示有明显个体差异,平均为37.90±11.26ng/ml。服药后24小时的血药浓度范围为9.22—23.97ng/ml,平均14.95±5.42ng/ml。口服单剂6mg左旋“18-甲”后血药消除曲线呈二室开放模型。服药后2—12小时为快速分布相,其半衰期(t1/2α)平均为2.71±1.37小时,消除半衰期(t1/2β)平均为45.65±17.95小时,血中左旋“18-甲”浓度降至低于100pg/ml所需时间为13.3天,提示药物在体内无明显积蓄。另选8名健康育龄妇女,连续给药3次,每次间隔23天,分别于给药前及给药后取血样测定左旋“18-甲水平。所有对象的三个用药周期中均于服药后1天内达血药峰值,于服药后16天血中“18-甲”浓度基本已低于可检出水平,表明连续三次口服6mg左旋“18-甲”后在体内亦无明显积蓄。三次口服给药后的平均消除半衰期分别为1.67.1,59、1.69天,表明连续给药后其代谢速率无明显改变。第2.3次服药后所达血药峰值无明显差异,但明显较首次给药后高,这可能是由于制剂中所含炔雌醚成份作用于肝脏引起血浆SHBG水平升高所致。 10 healthy women of childbearing age, on the fifth day of menstruation oral L-18 “A” 6mg. Venous blood was taken before taking the medicine and at different times after taking the medicine, and the level of “18-A” in the blood was measured by radioimmunoassay. The mean peak time of blood concentration of L-18-A was 3.20 ± 1.93 (M ± SD, the same below) hours, and the peak of blood plasma showed significant individual difference with an average of 37.90 ± 11.26ng / ml. Serum concentrations ranged from 9.22 to 23.97 ng / ml at 24 hours post-dose with an average of 14.95 ± 5.42 ng / ml. Oral a single dose of 6mg L-18-A “blood drug elimination curve showed a two-compartment open model. The average half-life (t1 / 2α) was 2.71 ± 1.37 hours and the elimination half-life (t1 / 2β) averaged 45.65 ± 17.95 hours. The concentration of levo ”18-A“ in blood decreased to The time required for less than 100 pg / ml was 13.3 days, suggesting no significant drug accumulation in the body. Another eight healthy women of childbearing age, continuous administration of three times, each time interval of 23 days, respectively, before and after administration of blood samples were taken for determination of levonorrhea. ”“ All three subjects in the medication period were taking After 1 day, the blood peak was reached, and the concentration of ”18-A" in the blood was basically lower than the detectable level 16 days after taking the medicine, indicating that there was no significant accumulation in the body after 6 consecutive doses of 6mg L-18-A The average elimination half-life after oral administration was 1.67.1, 59 and 1.69 days, respectively, indicating no significant changes in the metabolic rate after continuous administration. The peak plasma levels after the 2.3 administration showed no significant difference, but significantly higher than the first administration After the drug is high, this may be due to the composition contained in the role of ethinylestradiol in the liver caused by elevated levels of plasma SHBG.
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