Hrushesky W J, Borch R, Levi F
Clin Pharmacol Ther. 1982 Sep;32(3):330-9. doi: 10.1038/clpt.1982.168.
Free platinum urinary excretion kinetics after a 30-min infusion of 60 mg/m2 IV cis-diamminedichloroplatinum (C) were studied during 51 monthly courses of C therapy in 11 patients suffering from a variety of advanced malignancies. Each patient received half of his or her treatment course at 6:00 A.M. and 6:00 P.M. Initial treatment time was randomly assigned and subsequent treatment times were alternated. Each C infusion was accompanied by 4100-ml 5% dextrose and 0.45% NaCl solution given intravenously. Evening C infusion resulted in greater urine output, lower peak urinary platinum concentrations, and lower areas under the curve of cisplatin concentration. While the normal circadian rhythm characteristics of body temperature were not altered by changing the C infusion time, the circadian rhythm characteristics of urine volume 1 mo after treatment were significantly disrupted by morning, but not by evening, C. We conclude: (1) that since the kinetics of certain drugs may be affected by the time of administration, kinetic studies should be performed and reported in a time-qualified fashion, and (2) that it is reasonable to expect that, since kinetic parameters are important in determining drug toxicity and effect, these too may vary predictably during the day.
在11例患有各种晚期恶性肿瘤的患者接受51个疗程的顺二氯二氨铂（C）治疗期间，研究了静脉输注60mg/m²的C 30分钟后铂在尿液中的排泄动力学。每位患者在上午6:00和下午6:00接受其一半的治疗疗程。初始治疗时间随机分配，随后的治疗时间交替进行。每次C输注均伴有静脉输注4100ml 5%葡萄糖和0.45%氯化钠溶液。晚上输注C导致尿量增加、尿铂峰值浓度降低以及顺铂浓度曲线下面积减小。虽然改变C输注时间并未改变体温的正常昼夜节律特征，但治疗1个月后尿量的昼夜节律特征在上午输注C时受到显著干扰，而在晚上输注C时未受干扰。我们得出结论：（1）由于某些药物的动力学可能受给药时间影响，动力学研究应以有时间限定的方式进行并报告；（2）由于动力学参数在确定药物毒性和效果方面很重要，可以合理预期这些参数在一天中也可能有可预测的变化。
