丹参素静脉注射后在兔眼房水和血浆中的药物代谢动力学研究  

Drug dynamics research of salvia miltiorrhiza in rabbit plasma and aqueous humor after intravenous injection

作　　者：张丽琼[1] 于永斌[1] 李明生[1] 齐慧萍[1] 崔浩[1] 

机构地区：[1]哈尔滨医科大学附属第一医院眼科医院,150001

出　　处：《中华眼科杂志》2013年第9期835-840,共6页Chinese Journal of Ophthalmology

基　　金：黑龙江省自然科学基金（D200949）;哈尔滨市科技局资助项目（2007RFQXS090）;黑龙江省教育厅科学技术研究项目（11541219）;黑龙江省卫生厅科研项目（2007-22）

摘　　要：目的探讨丹参素通过血眼屏障的能力及药物代谢动力学特点。方法实验研究。72只白兔随机数字表法分为对照组（6只）、血浆组（6只，再分为10个亚组，每亚组6只，对应给药后10个时间点）及房水组（60只）。对照组0．85％生理盐水20ml静脉注射，其余两组静脉注射不同浓度的丹参素，于注射后不同时间取血浆和房水，采用高效液相色谱法检测丹参素的药物代谢动力学参数。采用DAS2．0版药物代谢动力学软件进行房室拟合，并计算各药物代谢动力学参数。结果丹参素血浆质量浓度符合三室模型。消除半衰期为5．661min，峰浓度为727．29mg／L，达峰时间为0min，清除率为0．797L·min^-1·kg^-1。房水质量浓度符合二室模型，消除半衰期为147．663min，峰浓度为38．62mg／L；达峰时间为25min，清除率为3．476L·min^-1·kg^-1。对照组血浆、房水中未检测到丹参素。结论丹参素静脉注射后可以通过血眼屏障，在房水中消除较慢，并且能长时间在房水中保持一定浓度。Objectives To assess the permeability of Danshensu at blood-ocular barrier and its characteristics of pharmacokinetics by respectively measuring the concentrations of Danshensu in blood plasma and aqueous humor of the rabbit with the high performance liquid chromatography （HPLC）. Methods It was an experimental study. Seventy-two white rabbits were split into three groups： control group （6 rabbits）, plasm group （6 rabbits） and aqueous humor group （60 rabbits）. After 0.85% salt water （control group）or salvia miltiorrhiza （1.0 g/kg） （plasma and aqueous group） was injected into the vein of auris-edge. Samples of blood and aqueous humor were obtained for analysis . The analytical column was a BDS C18 stainless steed column （5 I-Lm, 4. 6 mm ~ 250 mm）; Precolumn： YWGCls; the mobile phase consists of acetonitrile and 0. 01 mol/L KH2PO4 （ 8：92, adjusted to pH = 2. 8 with phosphoric acid）. The UV detector was set at 279 nm; the flow rate was 1.0 ml/min; and the column temperature was ordinary temperature. Results The plasma concentration-time curves of Salvia miltiorrhiza fitted three-compartment model, t1/2 [3 （elimination half time） ：5. 661 rain; Cmax（peak concentration） ：727.29 mg/L; Tmax（peak time ）：0 min. The aqueous humor concentration-time curves fitted two-compartment model, t1/2 [3： 147. 663 rain; Cmax： 38. 62 mg/L; Tmax： 25 min. Conclusions HPLC is a sensitive, specific and accurate method that can be used in pharmacokinetics research on ocular tissue of rabbit for Danshensu, Salvia miltiorrhiza that is dissolvable in water can pass through the blood-ocular barrier after intravenous injection with a relatively stable concentration of danshensu in aqueous humor resulting from a slow rate of removal.

关 键 词：丹参 药代动力学 眼房水 血房水屏障 色谱法 高压液相 兔 

分 类 号：R285.6[医药卫生—中药学]