顺铂在家兔体内的时间药动学

目的　研究顺铂在家兔体内药代动力学的时间节律特征。方法　实验动物饲养在标准环境中，分别于昼夜不同时辰一次给药，以原子吸收光谱法测定给药后不同时刻血中铂浓度，并将通过３ Ｐ８７ 程序计算所得的主要药动学参数按平均余弦法进行处理。结果和结论　顺铂的主要药动学参数呈一定昼夜变化，其中消除相半衰期（ Ｔ１２ β） 、表观分布容积（ Ｖｄ） 、曲线下面积（ Ａ Ｕ Ｃ） 、清除率（ Ｃ Ｌ） 等波动较大，峰、谷值之间具显著或非常显著差异。上述各参数昼夜节律峰值期分别在０２ ：１３ 、０４ ：４５ 、００ ：３７ 和１３ ：１０

Chronopharmacokinetics of cisplatin in rabbits *

AIM To investigate the chronobiological regularities of pharmacokinetics of cisplatin(CDDP). METHODS Rabbits were housed in a room of temperature controlled at(22 5±0 5)℃, relative humidity at 55%±5%, and a standardized regimen of light/dark (LD) 12/12 (light on from 07:30～19:30 h) with sound insulated. Food and water were freely available. The agent was administered at different time points in the LD cycle respectively. Mean cosinor method was used to characterize the circadian rhythm parameters, and 3P87 program to analyze the pharmacokinetic data. RESULTS AND CONCLUSION Dispositions of the agent in the body were time dependent. CDDP was eliminated faster when it was administered intravenously (iv) in the late activity span. At this circadian stage, T 12 β was relatively shorter (23 51±6 37 h) and CL was faster(0 10±0 01 L·kg -1 ·h -1 ). AUC value was(57 80±6 33) mg·h -1 ·L -1 . When CDDP was administered to rabbits in the late activity span, the agent was exhibited its shorter retention time and less accumulation in their body than at other circadian time. Peak time of T 12 β, V d, AUC and CL was 02:13, 04:45, 00:37 and 13:10, respectively.