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目的:研究异环磷酰胺(ifosfamide,IFO)与艾迪注射液联用,是否对其代谢有影响,为临床合理用药的安全性和有效性提供参考依据。方法:对6只兔子采用随机自身交叉对照试验设计,对照组予生理盐水10 mL和异环磷酰胺0.11 g.kg-1用生理盐水稀释至10 mL,实验组予艾迪注射液1 mL.kg-1和异环磷酰胺0.11 g.kg-1均用生理盐水稀释至10 mL;均通过耳缘静脉注射给药。采用C18固体萃取小柱处理血样,然后用高效液相色谱法测定异环磷酰胺的浓度,最后计算并比较2组药动学参数及生物利用度。结果:对照组和实验组AUC0-∞分别为(140.53±39.26),(120.02±25.89)mg.L-1.h-1,AUC0-t分别为(128.37±34.26),(119.18±25.51)mg.L-1.h-1,Cmax分别为(158.63±16.35),(132.61±21.07)mg.L-1;实验组的相对生物利用度F0-∞为(91.13±34.50)%,F0-t为(97.62±32.59)%;实验组生物利用度小于对照组,两组非生物等效。结论:两组异环磷酰胺在兔体内的代谢均符合二室房室模型。实验组IFO的生物利用度显著性小于对照组,提示艾迪对IFO在兔体内药代动力学有显著性影响;艾迪注射液还使IFO在兔体内的血药浓度明显降低,推测艾迪注射液可能使其疗效也有所降低。
Objective: To study if ifosfamide (IFO) in combination with Aidi Injection can affect its metabolism and provide a reference for the safety and effectiveness of rational drug use. Methods: Six rabbits were randomized cross-self-controlled trial design. The control group was treated with 10 mL saline and ifosfamide 0.11 g.kg-1 diluted to 10 mL with normal saline, and 1 mL Aidi injection in the experimental group. kg-1 and ifosfamide 0.11 g.kg-1 were diluted to 10 mL with normal saline; intravenous injection through the ear. Blood samples were treated with C18 solid-phase extraction cartridges, and then the concentration of ifosfamide was determined by HPLC. Finally, the pharmacokinetic parameters and bioavailability were calculated and compared. Results: The AUC0-∞ of the control group and the experimental group were (140.53 ± 39.26) and (120.02 ± 25.89) mg.L-1.h-1 respectively, and the AUC0-t were 128.37 ± 34.26 and 119.18 ± 25.51 mg . The relative bioavailability (F0-∞) in the experimental group was (91.13 ± 34.50)%, F0-t (97.62 ± 32.59)%. The bioavailability of the experimental group was less than that of the control group, and the two groups were not bioequivalent. Conclusion: The two groups ifosfamide metabolism in rabbits are in line with two-compartment atrioventricular model. The bioavailability of IFO in the experimental group was significantly lower than that of the control group, suggesting that Addison had a significant effect on the pharmacokinetics of IFO in rabbits. Aidi injection also significantly reduced the serum concentration of IFO in rabbits. Injection may also reduce its efficacy.