用生物检定法研究力达霉素在小鼠和犬的药代动力学

目的用生物检定法测定力达霉素活性浓度和研究其药代动力学。方法体外细胞毒检测法测定血清力达霉素浓度。结果方法学确证基本符合药代动力学研究要求。小鼠iv力达霉素100,50和10 μg·kg^-1后浓度曲线符合二房室模型，α和β相t_1/2分别是0.77~1.8 min和5.6~7.2 min。AUC分别是2 851.3，887.8和166.4 μg·min·L^-1，随剂量非线性增加。AUC增加和抑瘤疗效增长趋势相似。犬iv力达霉素12 μg·kg^-1后浓度低并迅速下降，AUC仅16 μg·min·L^-1，比小鼠浓度低和消除快。首次给药后15 d进行第2次给药，第2次给药浓度低于首次。结论用生物检定法成功测定血清力达霉素浓度和研究其药代动力学。力达霉素药代动力学存在种属、单次及多次给药差别。

Studies on the pharmacokinetics of lidamycin in mice and dogs using bioassay

AIM: A bioassay method was established for the determination of active concentrations of lidamycin and studied its pharmacokinetics in mice and dogs. METHODS: Cytotoxicity of lidamycin in vitro was used to determine drug serum concentrations in vivo. RESULTS: Validity of methodology met the requirements of pharmacokinetic study. The concentration-time profile in mice after iv lidamycin of 100, 50 and 10 microg x kg(-1) was best fitted with 2-compartmental model with T1/2alpha and T1/2beta of 0.77-1.8 min and 5.6-7.2 min, respectively. The AUC were 2851.3, 887.8 and 166.4 microg x min x L(-1), respectively and increased with dose nonlinearly. There were similar trends between AUC and the potency of tumor growth inhibition. After iv lidamycin of 12 microg x kg(-1) in dogs, the concentrations of lidamycin decreased rapidly and the AUC was 16 microg x min x L(-1), which were lower and quicker than those in mice. The levels in serum after second administration at day 15, were lower than those of the first. CONCLUSION: Active concentrations and pharmacokinetics of lidamycin were obtained by bioassay method successfully. There are species differences and single and multi-dosing differences in the pharmacokinetics of lidamycin.