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本文报告了11例志愿者服用单剂量(±)、(+)及(-)棉酚后的药代动力学以及11名临床志愿者接受(±)棉酚抗生育试验8个月内的血药浓度和临床效应的平行观察结果。发现(±)棉酚在人体内的半衰期长达116.9h,无抗生育作用的(+)棉酚在体内的命运和(±)棉酚相似,而有抗生育活性的(-)棉酚的半衰期仅为2.8h。临床服药者在起初的两个月内(20mg/d),棉酚血药浓度有逐步蓄积现象,以后由于给药间隔延长(50mg/周),“平均”血药浓度维持在低水平上。实验证明在体内蓄积的主要是(+)棉酚。服药两个月末,精子计数才显著下降,3—4个月精子计数为零,以后略有回升。观察8个月内,服药者血清钾未见递减趋势。作者认为,棉酚的临床抗生育作用,不是通过药物在体内的蓄积,而是通过效应的积累体现出来的,这种情况也与棉酚抗生育作用的细胞毒性质相吻合。因此,适当增加单剂用药量,延长给药间隔时间,或用(-)棉酚代替(±)棉酚,都有可能在保持同等疗效的情况下,减轻其毒副反应。
This article reports the pharmacokinetics of 11 volunteers taking a single dose of (±), (+), and (-) gossypol and 11 clinical volunteers receiving blood within 8 months of the (±) gossypol resistance test Parallel observations of drug concentration and clinical effect. (±) gossypol was found to have a half-life of 116.9 h in the human body. The fate of (+) gossypol without anti-fertility in vivo was similar to that of (±) gossypol, while the activity of (-) gossypol The half-life is only 2.8h. During the first two months (20 mg / d) of clinical medication, there was a gradual build-up of gossypol plasma concentrations, with subsequent “mean” plasma concentrations remaining low due to prolonged dosing intervals (50 mg / week). Experiments show that the main accumulation in the body is (+) gossypol. At the end of the two months of taking the medicine, the sperm count decreased significantly, and the sperm count was zero in 3-4 months, then rebounded slightly. Observed within 8 months, medication serum potassium did not show a decreasing trend. The author believes that the clinical anti-fertility effect of gossypol, not through the accumulation of drugs in the body, but through the accumulation of effects embodied in this situation is also consistent with the cytotoxicity of gossypol anti-fertility consistent. Therefore, appropriate to increase the dose of a single dose, to extend the interval between administration, or (-) gossypol instead of () gossypol, are likely to maintain the same effect in the case, reduce its toxicity.