用生物检定法研究力达霉素在小鼠和犬的药代动力学  

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

作　　者：陈淑珍[1] 汤仲明[2] 甄永苏[1] 

机构地区：[1]中国医学科学院,中国协和医科大学医药生物技术研究所,北京100050 [2]军事医学科学院放射医学研究所,北京100850

出　　处：《药学学报》2004年第9期700-704,共5页Acta Pharmaceutica Sinica

基　　金：国家"十五"重大科技专项"创新药物和中药现代化"资助课题(2002AA223107).

摘　　要：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10μg·kg-1后浓度曲线符合二房室模型,α和β相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166.4μg·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16μg·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。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 10μg · kg-1 was best fitted with 2-compartmental model with T1/2αand T1/2β of 0. 77 - 1. 8 min and 5.6-7.2 min, respectively. The AUC were 2 851. 3, 887. 8 and 166. 4 μg · min· 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 12μg · kg-1 in dogs, the concentrations of lidamycin decreased rapidly and the AUC was 16μg· min · 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.

关 键 词：力达霉素 细胞毒作用 生物检定法 药代动力学 

分 类 号：R282.71[医药卫生—中药学] R917.101[医药卫生—中医学]