哌仑西平滴眼剂在兔房水中的药代动力学研究

The pharmacokinetics of prienzepine in the aqueous humor of rabbits

目的 :研究哌仑西平滴眼剂在兔眼房水中的药代动力学 ,为其临床开发提供依据。方法 :将 4 0只兔随机分为8组 ,每组 5只兔。配制不同pH值和不同粘度的哌仑西平滴眼剂 ,其中哌仑西平浓度均为 5 %。单眼单次滴入兔眼结膜囊后 ,分别于 8个时间点抽取房水 ,应用高效液相色谱法(HPLC)测定房水哌仑西平浓度随时间的变化情况 ,并每隔两周更换处方给药。结果 :哌仑西平难以透过角膜到达眼内。随着pH值的降低 ,哌仑西平角膜透过率逐渐提高。滴眼剂的粘度对角膜透过率无明显作用。结论 :哌仑西平在临床开发中需要改变剂型 。

Objective:To study the pharmacokinetics of pirenzepine in the aqueous humor of rabbits after a single dose of pirenzepine solution.Methods:The concentrations of pirenzepine in the aqueous humor were determined at different time intervals after instilling into the cul de sac of 40 rabbits by high pressure liquid chromatography(HPLC). Four formulations(pH=3,5 and 7,hydrogel concentration=0;pH=7,hydrogel concentration=2%) containing 5% pirenzepine base equivalents were administered to the rabbits.Results:It is hard for Pirenzepine to penetrate the cornea. The penetration rate was found to dependent on the pH of pirenzepine solution. The lower the pH,the higher the rate. Variation of the viscosity of the solution showed no effects on the penetration.Conclusion:Novel dosage forms of pirenzepine with high penetration rate must be developed if used to prevent myopia clinically.