毛果芸香碱透明质酸钠缓释滴眼剂在兔眼房水中的药代动力学研究

目的探讨0.5%毛果芸香碱透明质酸钠缓释滴眼剂滴眼后眼部的药代动力学特征,评价其相对生物利用度.方法选择健康白兔100 只,随机分为10个实验组和10个对照组,每组5只兔(10只眼).各实验组兔双眼结膜囊内均滴入0.5%毛果芸香碱透明质酸钠缓释滴眼剂50 μl,各对照组兔双眼亦滴入1%毛果芸香碱滴眼液50 μl.分别于给药后5、10、20、30、40、60、90、120、150及180 min抽取房水并对其定量分析.用二氯甲烷提取房水中的药物,采用反相高效液相色谱法(HPLC)测定房水中的药物浓度.药代动力学参数采用3p87药代动力学计算软件计算机拟合求得.结果采用反相HPLC法可以将毛果芸香碱与其它杂质很好分离,最低检测浓度为0.025 μg/ml.毛果芸香碱在房水中的回收率平均为98.2%.实验组和对照组给药后药物房水达峰时间分别为10 min和20 min, 达峰浓度分别为4.46 μg/ml和2.25 μg/ml, 药物消除半衰期分别为31.83 min和22.98 min.实验组药物的房水浓度-时间曲线下面积(AUC0～180)是对照组的1.75倍.实验组房水药物达峰浓度是对照组的1.98倍(P<0.05).结论 0.5%毛果芸香碱透明质酸钠缓释滴眼剂与1%毛果芸香碱滴眼液比较,达峰时间提前,达峰浓度增高,消除半衰期延长,提示其相对生物利用度提高,作用时间延长.

Ocular pharmacokinetics of 0.5% pilocarpine with sodium hyaluronate in rabbits

OBJECTIVE: To compare the pharmacokinetics of 0.5% pilocarpine containing sodium hyaluronate with 1% generic pilocarpine solution. METHODS: One hundred albino rabbits were divided into 20 groups, each consisting of 5 animals. Ten groups received 0.5% pilocarpine containing sodium hyaluronate and 10 groups received 1% generic pilocarpine solution as control. The aqueous humor was withdrawn at 5, 10, 20, 30, 40, 60, 90, 120, 150, and 180 min after instillation. The drug was extracted from aqueous humor with dichloromethane and was detected by reversed phase high performance liquid chromatography (HPLC). RESULTS: The average recovery rate of pilocarpine from aqueous humor was 98.2%. The minimum detectable concentration was 0.025 micro g/ml. The peak concentration and half-life of pilocarpine in aqueous humor were 4.46 micro g/ml at 10 min and 31.83 min, respectively, in the experimental group. Whereas, the peak concentration and half-life of pilocarpine in aqueous humor were 2.25 micro g/ml at 20 min and 22.98 min, respectively, in the control group. The peak concentration of pilocarpine in aqueous humor in the experimental group was 1.98 (P < 0.05) times higher than the control group. The area under curve of the drug concentration-time (AUC(0 - 180)) in the experimental group was 1.75 times higher than the control group. CONCLUSION: Pilocarpine (0.5%) containing sodium hyaluronate significantly increased the peak concentration of pilocarpine, shortened the time of reaching peak concentration and prolonged the half-life in aqueous humor. These results indicate that 0.5% pilocarpine with sodium hyaluronate significantly increases ocular bioavailability of pilocarpine.