摘要
目的研究哌仑西平脂质体结膜囊内应用后在家兔眼部的药代动力学。方法48只家兔随机分为磷酸盐缓冲液组和脂质体组,分别于给药后0.5、1、2、4、6、8、10、12h取材,采用高压液相色谱技术进行测定,3P97软件拟合药代动力学参数,统计学分析采用t检验和单因素方差分析。结果脂质体组各组织中哌仑西平的质量浓度和质量分数较磷酸缓冲液组高,用药2h后各时间点各组织间相比均有显著统计学差异(P<0.01),它们在各组织中的变化均呈一室开放模型。同一种组织中除脉络膜的消除半衰期外,其余组织各药代动力学参数间(Cmax、t1/2、MRT、AUC)差异有统计学意义(P<0.05)。巩膜中哌仑西平的质量分数高于脉络膜和视网膜(P<0.05)。结论哌仑西平脂质体眼部应用有缓释效应,生物利用度高,其很可能是以非角膜途径吸收为主进入眼内的。
Objective We have report the preparation of pirenzepine liposome in previous paper. The purpose of this study is to investigate the pharmacokinetics of pircnzcpine in various tissues of rabbit eyes after topical application of pirenzepine liposome. Methods Forty-eight New-Zealand rabbits were randomly divided into pirenzepine phosphoric acid buffer and pirenzepine liposome group and then subdivided into 8 groups according to the different scarifying time in both groups respectively. 0.3% pirenzepine phosphoric acid buffer and 0.3% pirenzepine liposome were topically applied in both eyes of each rabbit respectively. The levels of pirenzepine in aqueous humor, vitreous body, retina, ehoroids and selera were examined at 0.5, 1 hour, 2, 4, 6, 8, 10 and 12 hours after topical application of two drugs by high performance liquid chromatography with imipramine as an internal standard. All the pharmaeokinetie parameters in the same tissue after application of two drugs were compared, and the concentration of pirenzepine in the retina, ehoroid and selera were analyzed. Results The concentration of pirenzepine in aqueous humor, vitreous body, retina, ehoroid and selera was higher in pirenzepine liposome group than that in pirenzepine phosphoric acid buffer group 2 hours later with a significant difference between two groups （P 〈 0.01）. The concentration of pirenzepine in all the ocular tissues was subjected to one-compartment open model after topical application of two drugs. All the pharmacokinetic parameters in the same tissue, including Cmax, t1/2. MRT, and AUC, exhibited statistically significant difference （P 〈 0.05） except for the t1/2 in choroids （P 〉 0.05） between two groups. The pirenzepine concentration in sclera was higher than that in retina and choroids （P 〈 0.05）. Conclusion The sustained release of pirenzepine liposome and its bioavailability are higher of than that pirenzepine phosphoric acid buffer followed the topical administration in rabbit eyes. These drugs may enter into the intraocular tissue mainly by the non-cornea pathway after topical application.
出处
《眼科研究》
CSCD
北大核心
2006年第2期132-135,共4页
Chinese Ophthalmic Research
