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目的 :对氟尿嘧啶植入剂体外溶出和家兔体内药物动力学进行研究。方法 :分别用交联剂法和辐射法制备以聚甲基丙烯酸羟乙酯 [Poly(2 -hydroxyethylmethacrylate) ,p(HEMA) ]和胶原蛋白 (Collagen)复合物 [以下简称p - (HEMA) -胶原 ]为基质的氟尿嘧啶缓释植入剂 ,体外溶出在 37℃蒸馏水中进行 ,将植入剂植入家兔胸棘肌内进行体内药物动力学研究 ,用注射剂作为对照。结果 :植入剂的体外释药过程符合Higuchi动力学 ,交联剂法制备植入剂的体外溶出参数为t5 0 % =7.2h ,t90 % =2 3.9h ,家兔体内药动学参数为 :AUC =2 2 2 .6 19h·μg·ml- 1 ,MRT =33.6 74h ,Ka =0 .5 37h- 1 ;辐射法制备植入剂的体外溶出参数为t5 0 % =9.9h ,t90 % =32 .7h ,家兔体内药动学参数为 :AUC =2 6 8.6 6 6h·μg·ml- 1 ,MRT =41.70 4h ,Ka =0 .334h- 1 。结论 :用交联剂法和辐射法制备的p - (HEMA) -胶原可以作为氟尿嘧啶的植入缓释载体。
OBJECTIVE: To study the in vitro dissolution of fluorouracil implants and the pharmacokinetics of rabbits in vivo. Methods: Poly (2-hydroxyethylmethacrylate) (p (HEMA)] and Collagen complex [hereinafter referred to as p - (HEMA) - Collagen] as the substrate fluorouracil sustained-release implants in vitro dissolved in distilled water at 37 ℃, the implants implanted intramuscular injection of rabbit breast thoracic muscle pharmacokinetics, with injection as a control. RESULTS: The in vitro release of the implants was in accordance with Higuchi kinetics. The in vitro dissolution parameters of the implants prepared by the crosslinking agent method were t5 0% = 7.2h and t90% = 2 3.9h. The pharmacokinetic parameters in rabbits were : AUC = 22.66 19h · μg · ml-1, MRT = 33.6 74h, Ka = 0.537h-1. The in vitro dissolution parameters of the implants prepared by irradiation were t5 0% = 9.9h, t90% = 32 .7h, the pharmacokinetic parameters in rabbits were: AUC = 26.66 6 6 μg · ml-1, MRT = 41.70 4h, Ka = 0.334h-1. CONCLUSION: The p - (HEMA) - collagen prepared by the cross - linking method and the radiation method can be used as the sustained release carrier of fluorouracil.