盐酸川芎嗪滴眼液在兔眼房水中的药动学研究

Pharmacokinetic study on ligustrazine hydrochloride eye drops in aqueous humor of rabbits following topical administration

目的探讨兔眼局部应用盐酸川芎嗪滴眼液后在房水中的药代动力学特征。方法将新西兰白兔27只,随机分为9组,分别于兔眼滴入盐酸川芎嗪滴眼液50μL,并于不同时间点抽取房水。采用高效液相色谱法测定盐酸川芎嗪浓度,DAS2.1.1软件拟合药代动力学参数。结果兔眼滴用盐酸川芎嗪后,盐酸川芎嗪在房水中的浓度变化呈二室模型,盐酸川芎嗪在房水中的药代动力学参数分别为达峰浓度(Cmax),(16.202±2.564)μg/mL;达峰时间(Tmax),0.083 h;吸收相半衰期(t1/2α),(0.509±0.179)h;消除相半衰期(t1/2β),(0.857±0.278)h;曲线下面积(AUC),(14.584±2.950)μg.h/mL。结论盐酸川芎嗪滴眼后能快速渗透到房水中,且浓度较高,但消除也较快。

AIM To study the pharmacokinetics of ligustrazine hydrochloride in aqueous humor following topical administration in rabbits.METHODS Twenty-seven New-England rabbits were divided randomly into nine groups.The rabbits of each group were topically applied with 50 μL ligustrazine hydrochloride eye drops in both eyes respectively and aqueous humour were collected at different time after topical application of ligustrazine hydrochloride eye drops.The concentration of ligustrazine hydrochloride in aqueous humour was examined by HPLC.Pharmacokinetic parameters were obtained with DAS2.1.1 software.RESULTS The concentration of ligustrazine hydrochloride in aqueous humour after topical application was subjected to two-compartment open model.The pharmacokinetic parameters of ligustrazine hydrochloride in aqueous humour were： Cmax（16.202±2.564） μg/mL,Tmax 0.083 h,t1/2α（0.509±0.179） h,t1/2β（0.857±0.278） h,AUC（14.584±2.950） μg·h/mL,respectively.CONCLUSION Ligustrazine hydrochloride has a good permeability and high concentration in aqueous humor of rabbit after ocular administration.However,the clearance of it in aqueous humor is fast.