新目安眼用即型凝胶与普通凝胶兔眼内药动学特性比较研究

Comparative Research Between the New Mu-an In-situ Forming Eye Gel and the Common Gel on the Transit Pharmacokinetics Character in Rabbit Aqueous Humor

目的探索新目安眼用即型凝胶相变过程对兔眼内房水中药物药动学特性的影响,并与普通凝胶比较,评价该即型凝胶的剂型特征。方法以新西兰家兔为试验对象,采用眼部给予新目安眼用即型凝胶(存在相变过程)和普通凝胶后,按时间点取房水,测定更昔洛韦含量,建立药物在房水中的药动学方程,计算体内药动学参数,比较两者的差别。结果新目安眼用即型凝胶房水中更昔洛韦药动学方程为C=18.94×e^(-0.015 4t)-18.94×e^(-0.07985t),普通凝胶房水中更昔洛韦药动学方程为C=15.42×e^(-0.015 3 t)-15.42×e^(-0.048 8 t),说明两者在兔眼内的药动学机制相同。从各药动学参数比较分析,新目安眼用即型凝胶由于相变过程使达峰时间仅为25.51min,达峰浓度高达10.31μg·mL^(-1),吸收半衰期缩短为8.679min,AUC提高到992.4μg·mL^(-1)·min,而普通凝胶达峰时间为34.63 min,达峰浓度仅为6.232μg·mL^(-1),吸收半衰期为14.20 min,AUC仅为691.4μg·mL^(-1)·min。结论即型凝胶相转变过程能将相变潜能(△H)转变成药物角膜渗透的动能,可最大限度发挥药效。

OBJECTIVE To evaluate the characteristic of the dosage form of the new Mu-an in-situ forming eye gel by compare the effect of the drug transit pharmacokinetics character in rabbit aqueous humor of the phase transition process with common gel. METHODS Taken New Zealand rabbits as research objects, after giving new Mu-an in-situ forming eye gel(had phase transition process) and common gel in ocular, obtained aqueous humor in different time points, detected the content of ganciclovir, established the transit pharmacokinetics equations of drug in aqueous humor, calculated the transit pharmacokinetics parameters of drugs in vivo, made a comparison between the new Mu-an in-situ forming eye gel and the common gel. RESULTS The transit pharmacokinetics equations of ganciclovir in aqueous humor of new Mu-an in-situ forming eye gel was C=18.94×e-0.015 4 t-18.94×e-0.079 85 t, the transit pharmacokinetics equations of ganciclovir in aqueous humor of common gel was C=15.42×e-0.015 3 t-15.42×e-0.048 8 t. It could explain that both two gel had the same transit mechanism in aqueous humor of rabbits. Through the comparative analysis of different pharmacokinetic parameters, it showed that time to peak of new Mu-an in-situ forming eye gel was 25.51 min, the concentration to peak was 10.31 μg·mL-1, t1/2 was 8.679 min and the AUC was 992.4 μg·mL-1·min, while for common gel, the time to peak was 34.63 min, the concentration to peak was 6.232 μg·mL^-1, t1/2 was 14.20 min and the AUC was 691.4 μg·mL^-1·min. CONCLUSION Phase transition energy(△H) turns into kinetic energy of drug permeate cornea in the phase transition process of in-situ gel, which can take pesticide effect for it to be as effective as possible.