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目的:研究异环磷酰胺在兔体内的药动学。方法:随机选用家兔6只,根据体质量予相应剂量的异环磷酰胺静脉注射,在5,10,20,30,45min及1,1.5,2,2.5,3,5,7h取血1mL。血清样品用C18固体萃取小柱处理,用高效液相测定药物浓度。所测定数据用3P97程序处理,以获得相关的药动学参数。结果:异环磷酰胺在2.5~200mg.L-1(r=0.999)范围内线性良好;绝对回收率在89.3%~93.6%之间。拟合的最佳房室模型为二室模型;测定的药动学参数为:tα/2=0.44±0.12h,tβ/2=5.3±3.1h,k21=0.25±0.43h-1,k10=1.2±0.4h-1,k12=0.39±0.50h-1,V=1.44±0.25L,CL=1.7±0.8L.h-1,AUC0-∞=140.5±39.3mg.L-1.h,AUC0-t=128.4±34.3mg.L-1.h。结论:异环磷酰胺在兔体内的代谢符合二室房室模型。
Objective: To study the pharmacokinetics of ifosfamide in rabbits. Methods: Six rabbits were randomly selected, according to the body weight of the corresponding dose of ifosfamide intravenous injection at 5,10,20,30,45min and 1, 1.5,2,2.5,3,5,7 h blood 1mL . Serum samples were processed on C18 solid-phase extraction cartridges and the drug concentrations were determined using HPLC. The measured data was processed with the 3P97 program to obtain the relevant pharmacokinetic parameters. Results: Ifosfamide had good linearity in the range of 2.5 ~ 200 mg.L-1 (r = 0.999); the absolute recoveries ranged from 89.3% to 93.6%. The best room model fitted was a two-compartment model. The measured pharmacokinetic parameters were: tα / 2 = 0.44 ± 0.12h, tβ / 2 = 5.3 ± 3.1h, k21 = 0.25 ± 0.43h-1, k10 = 1.2 ± 0.4 h -1, k12 = 0.39 ± 0.50 h -1, V = 1.44 ± 0.25 L, CL = 1.7 ± 0.8 Lh -1, AUC 0 -∞ = 140.5 ± 39.3 mg.L -1.h, AUC 0 -t = 128.4 ± 34.3 mg.L-1.h. Conclusion: Inosine cyclophosphamide metabolism in rabbits conforms to the two-compartment atrioventricular model.