葛根素经全身用药在兔眼房水和玻璃体中的药代动力学

Pharmacokinetics of Puerarin in the Aqueous Humor and Vitrious of Rabbit Eye Following Systemic Administration

目的:测定腹腔注射单次剂量的葛根素后不同时间点新西兰白兔眼房水、玻璃体中葛根素的浓度变化,探讨葛根素在兔眼房水和玻璃体中的药动学变化。方法:新西兰白兎随机分组,每只白兔腹腔注射葛根素80mg/kg,在用药前(0h)和用药后0.5、1、2、3、4、6、8、12、16、24h取房水液、玻璃体液,采用反相高效液相色谱法(RP-HPLC)进行测定。3P87软件拟合药动学参数。结果:腹腔注射葛根素后,其浓度在正常新西兰白兔房水、玻璃体呈开放式二房室模型。理论值:高峰浓度(Cmax)分别为1.61、0.09μg/ml,达峰时间(tmax)为1.68、1.81h,半衰期t1/2α为1.36、1.05h,t1/2β为19.72、15.18h,清除率(CL)分别为2.17、12.43L/h。实测值30min分别为(0.78±0.29)μg/ml、(0.06±0.02)μg/ml,2h达高峰,分别为(2.32±0.15)μg/ml、(0.12±0.04)μg/ml,随后逐渐下降,6h后房水中葛根素含量降至0.57μg/ml,玻璃体为0.05μg/ml,16h后,葛根素在房水和玻璃体中的浓度降至0.03μg/ml或以下。结论:本方法灵敏、特异、准确和快速,可用于房水、玻璃体中葛根素浓度的测定;葛根素通过腹腔注射能透过血-眼屏障进入房水、玻璃体,进入房水的葛根素药量较大,进入玻璃体的药量有限。

PUrpose： To study dynamic changes of puerarin in aqueous humor and vitreous humor of rabbit eye following a single dose intraperitoneal injection. Methods： Rabbits were randomly divided into 11 groups. Puerarin （80 mg/kg） was given by a single dose intraperitoneal injection. After the administration, the aqueous humor, vitreous were harvested at different time points and the concentration of puerarin was determined by reversed phase high performance liquid chromatography （ RP-HPLC ）. Results： The concentration-time data of puerarin in aqueous humor, vitreous was subject to two-compartment open model. The pharmacokinetic parameters were separately as following. Cmax=1.61,0.09 μg/Inl, tmax=1.68,1.81 h. t1/2α=1.36,1.05 h. t1/2β= 19.72,15.18 h. CL=2.17,12.43 L/h. The practical data of the concentration of puerarin in aqueous humor and vitreous humor that were detected was （0.78±0.29） μg/ml, （0.06±0.02）μg/ml at 30 min respectively and reach maximum concentration was （2.32±0.15）μg/ml,（0.12±0.04）μg/ml at 2 h. Then the concentration of puerarin in aqueous humor and vitreous humor was gradually decreased. The concentration of puerarin was 0.57 μg/ml in the aqueous humor, 0.05 μg/ml in the vitreous humor at 6 h. The concentration of puerarin declined to a lower point 0.03 μg/ml or below in aqueous humor and vitreous humor after 16 h. Conclusions： Using HPLC method to detect puerarin in the aqueous humor and vitreous humor was particular, accurate and sensitive. The puerarin can penetrate blood-ocular barrier to enter aqueous humor and vitreous humor. The concentration of puerarin in the aqueous humor was obviously more than that in the vitreous humor. The quantation of puerarin entering vitreouse humor was limited. The clearance of the compound were slower and half-life were longer in aqueous humor and vitreous, that can provide principle basis for treating eye diseases with puerarin by systemic administration. Eye Science 2006;22：275-279.