盐酸川芎嗪眼用温敏原位凝胶的制备及兔眼房水内药动学

Preparation of thermosensitive in situ gel containing ligustrazine hydrochloride for ophthalmic use and pharmacokinetics in aqueous humor of rabbit eyes

目的:制备盐酸川芎嗪眼用温敏凝胶并探讨其在家兔眼房水内的药动学特征。方法:以泊洛沙姆为温敏材料,制备盐酸川芎嗪眼用温敏原位凝胶。分别于兔眼中滴入眼用凝胶50μl,采用高效液相色谱法测定给药后不同时间兔眼房水中的盐酸川芎嗪的浓度,绘制药-时曲线,利用DAS 2.0药动学软件计算相关药动学参数。结果:盐酸川芎嗪眼用温敏原位凝胶在兔眼内的吸收和消除过程呈线性二室模型动力学特征,其动力学方程为C=5.47×e-0.599 t+4.98×e-0.173 t-9.91×e-1.670 t,tmax为1.4 h,Cmax为4.732 mg·L-1,吸收相半衰期t1/2 a为0.420 h,分布相半衰期t1/2α为1.157 h,消除相半衰期t1/2β为4.006 h,药时曲线下的面积AUC为31.984 mg·h·L-1。结论:此方法可用于测定房水中盐酸川芎嗪的浓度,为盐酸川芎嗪眼用温敏凝胶的药动学研究提供评价方法。

OBJECTIVE To prepare thermosensitive in situ gel containing ligustrazine hydrochloride for ophthalmic use and study its pharmacokinetic parameters in aqueous humor of rabbit eyes. METHODS The thermosensitive in situ gel of ligus- trazine hydrochloride was prepared using poloxamer 407 and poloxamer 188 as thermosensitive materials. The rabbits of each group were topically applied with 50 μl of thermosensmve m sltu gel in both eyes, and drug concentrations in aqueous humor were determined at different times by HPLC. Aqueous humor concentration-time curve was plotted and pharmaeokinetic pa- rameters were calculated by using DAS 2. 0 pharmacokinetics software. RESULTS Concentration of ligustrazine hydroehloride in aqueous humor after topical application was subject to two-compartment open model. The pharmacokinetie parameters of li- gustrazine hydrochloride in aqueous humor were as follows： tmax was l. 4 h, Cmax was 4. 732 mg·L^- 1 ,t1/2, was 0. 420 h, t1/2α was 1. 157 h, t1/2β was 4. 006 h, AUC was 31. 984 mg·h·L^-1 CONCLUSION This method can be used to determine concentrations of ligustrazine hydrochloride in aqueous humor of rabbit eyes, and suitable for pharmacokinetics study of ligustrazine hydro- chloride contained in thermosensitive in situ gel.