盐酸川芎嗪全身用药在兔眼房水中的药代动力学研究

Pharmacokinetic study on tetramethylpyrazine hydrochloride in aqueous humor of rabbits following intraperitoneal injection

目的 测定腹腔注射盐酸川芎嗪后不同时间新西兰白兔房水中的质量浓度变化 ,计算其药代动力学参数 ,研究药代动力学特点。方法 44只新西兰白兔随机分为 11组 ,各组每只白兔腹腔注射盐酸川芎嗪 80mg/kg ,在用药前( 0h)和用药后 0 2 5、0 5 0、0 75、1、1 5、2、3、5、8、12h取房水 ,采用反向高效液相色谱法进行测定。 3P87软件拟合药代动力学参数。结果 腹腔注射盐酸川芎嗪后 ,其质量浓度在正常新西兰白兔眼房水中呈开放式二房室模型 ,理论值达峰时间 (tmax)为 0 2 8h ,达峰质量浓度 (Cmax)为 13 73 μg/mL,半衰期t1 /2α为 0 42h、t1 /2 β为 3 97h ,清除率 (CL)为 1 3 4L/h。实测值 15min为 ( 11 91± 1 41) μg/mL,3 0min达高峰 ,其达峰质量浓度为 ( 18 71± 1 13 ) μg/mL ,随后逐渐下降 ,5h降至0 0 6μg/mL,8～ 12h房水几乎测不到。结论 本方法灵敏、特异、准确 ,可用于房水中盐酸川芎嗪质量浓度的测定 ;腹腔注射川芎嗪能透过血 -房水屏障进入房水 ,这一结果为川芎嗪全身用药治疗眼前部疾病提供了实验依据。

Objective To determine the concentration and dynamic changes of tetramethylpyrazine hydrochloride in aqueous humor following intraperitoneal injection in rabbits. Methods Forty-four New Zealand white rabbits were randomly divided into 11 groups.The aqueous humor were collected at 0,0.25,0.50,0.75,1,1.5,2,3,5,8 and 12 hours following intraperitoneal injection of 80 mg/kg of tetramethylpyrazine hydrochloride,and the concentration of tetramethylpyrazine was detected by reversed phase high performance liquid chromatography(RP-HPLC). Results The concentration-time data of tetramethylpyrazine hydrochloride in aqueous humor was subjected to two-compartment open model.The pharmacokinetics parameters were found to be as following: C max= 13.73 μg/mL,t max= 0.28 h,t 1/2α= 0.42 h,t 1/2β= 3.97 h and CL= 1.34 L/h.The observed concentration of tetramethylpyrazine hydrochloride in aqueous humor was 11.91± 1.41 μg/mL at 15 min,and the maximum concentration reached 18.71± 1.13 μg/mL at 30 min.The concentration of tetramethylpyrazine hydrochloride in aqueous humor was decreased gradually thereafter to a much lower concentration of 0.06 μg/mL at 5 hours and almost undetectable in 8-12 hours. Conclusion The method of RP-HPLC is specific,accurate and sensitive to the measurement of tetramethylpyrazine hydrochloride in aqueous humor.Tetramethylpyrazine can penetrate blood-aqueous barriers and enter aqueous humor.