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目的:研究猕猴单次和多次(7天)静脉推注加滴注(剂量比为 1:1)新型重组水蛭素变异体-2(rHV-2)的药代动力学和部分促凝血酶原时间(KPTT)变化.方法:交叉设计比较单次1,3和6 mg·kg~(-1)及多次3mg·kg~(-1)注射后血浆rHV-2浓度及KPTT.ELISA法测定血浆rHV-2.结果:浓度曲线形状和水平与推注量及滴注速率相关.推注后 C_(max)分别为 2.90,9.78和15.68 mg·L~(-1),随后分别稳定在0.73-0.86,1.94-2.04和5.41-5.59 mg·L~(-1),剂量间血浆rHV-2浓度有统计差别.AUC随剂量呈线性增大,剂量间清除率和各时间常数无统计差别.各剂量组KPTT比基线值明显延长,随剂量增加有延长趋势.结论:推注剂量和滴注速率对控制rHV-2水平起重要作用,这对临床试验优化给药方案有一定作用.
OBJECTIVE: To study the pharmacokinetics and pharmacokinetics of rHV-2, a single and multiple (7 days) intravenous bolus instillation of rHV-2 at a dose ratio of 1: 1, (KPTT) .METHODS: The plasma concentrations of rHV-2 and KPTT-ELISA were compared after single injection of 1, 3 and 6 mg · kg -1 and 3 mg · kg -1 The plasma concentration of rHV-2 was measured.Results: The shape and level of concentration curve were correlated with the amount of bolus and infusion rate.The Cmax after bolus injection were 2.90, 9.78 and 15.68 mg · L -1, respectively, 0.73-0.86, 1.94-2.04 and 5.41-5.59 mg · L -1 .The plasma concentrations of rHV-2 in plasma had statistical difference.The AUC showed a linear increase with dose, and there was no significant difference between the doses and the time constants .The KPTT of each dose group was significantly longer than the baseline value, with the increase of dose.Conclusion: The bolus dose and instillation rate plays an important role in the control of rHV-2 level, which may play a role in the optimization of drug delivery in clinical trials.