毛果芸香碱微乳滴眼剂及滴眼液在兔眼房水中的药代动力学研究

Ocular pharmacokinetics of pilocarpine micron emulsion in rabbits

目的 对２％ 毛果芸香碱微乳滴眼剂与２％ 毛果芸香碱滴眼液在兔房水中的药代动力学进行对比研究。方法 健康白兔６０ 只，随机分成２０ 组，１０ 个实验组，１０ 个对照组，每组３ 只兔（６只眼） 。对各实验组双眼结膜囊内准确滴入２％ 毛果芸香碱微乳滴眼剂５０ μｌ，对各对照组双眼同法滴入２ ％ 毛果芸香碱滴眼液５０ μｌ，分别于给药后５、１０、３０、４０、６０、９０ 、１２０、１８０、２４０ 及３６０ ｍｉｎ 时抽取房水。用二氯甲烷提取房水中的药物，采用反相高压液相色谱（ｈｉｇｈ ｐｒｅｓｓｕｒｅｌｉｑｕｉｄ ｃｈｒｏｍａｔｏｇｒａｐｈｙ，ＨＰＬＣ） 法测定房水中的药物浓度。结果 用反相ＨＰＬＣ 法可以将毛果芸香碱与其它杂质分离，最低检测浓度为０－０１ ｍｇ／Ｌ。２％ 毛果芸香碱微乳滴眼剂或滴眼液５０ μｌ 滴眼后，除５ ｍｉｎ 时间点外，其余各时间点毛果芸香碱微乳滴眼剂治疗组的房水药物浓度较毛果芸香碱滴眼液治疗组明显增高（ Ｐ＝ ０－０００ ３ ～０－０４２） 。微乳滴眼剂的药时曲线下面积是滴眼液的３ 倍，微乳滴眼剂的生物利用度比滴眼液高２ 倍。用微乳滴眼剂后６ ｈ，房水中仍可测出毛果芸香碱的浓度，而用滴眼液后３ ｈ，房水中已测不出毛果芸香碱?

Objective To compare the pharmacokinetics of pilocarpine micron emulsion with generic pilocarpine solution in the aqueous humor Methods 60 albino rabbits were used and were divided into 20 groups, each consisting of 3 animals 10 groups received 2% generic pilocarpine 50 μl as controls; 10 groups received 50 μl of 2% pilocarpine micron emulsion in the conjunctival sac The aqueous humor was withdrawn at 5, 10, 30, 40, 60, 90, 120, 180, 240 and 360 min after instillation The drug was extracted from aqueous humor with dichloromethane The drug was analyzed by reversed phase high pressure liquid chromatography(HPLC) Results Pilocarpine micron emulsion therapy gave higher aqueous humor concentration of the drug than drops at all time periods tested except 5 min time point ( P =0 0003～0 042) The area under curve of micron emulsion was 3 times as much as that of drops There was a two fold increase in ocular bioavailability of pilocarpine due to the therapy with micron emulsion Measurable amounts of drug following 2% micron emulsion were still observed at 360 min while drug levels at 180 min following 2% drop therapy were nil Conclusion Our study results demonstrated significantly increase in ocular bioavailability of pilocarpine due to the therapy with micron emulsion Our finding indicates that a novel topical preparation of pilocarpine incorporated in micron emulsion might serve as a long acting antiglaucoma agent, and less frequent applications are necessary with it than with conventional drops