新型钾通道开放剂(QO-58)在大鼠体内药代动力学研究  

Pharmacokinetic study of QO-58: a new potassium channel opener

作　　者：刘灿仿[1,2] 祁金龙[1] 张海林[1] 贾庆忠[1] 

机构地区：[1]河北医科大学药理学教研室,教育部血管与神经生物重点实验室,河北省新药药理毒理重点实验室,河北石家庄050017 [2]邢台医学高等专科学校药剂教研室,河北邢台054000

出　　处：《中国药理学通报》2014年第4期574-577,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30970659);教育部重点研究课题(No 208014);河北省卫生厅重点课题(No 20100034);河北省自然科学基金资助项目(No H2013206048);河北省科技支撑计划项目(No 12276405D);河北省教育厅优秀青年基金(No YQ2013033)

摘　　要：目的：建立一种新型高效M型钾通道开放剂（QO-58）体内检测方法,研究其在大鼠体内的药代动力学特征。方法大鼠灌胃（ ig,25、50、100 mg＆#183;kg-1）3个剂量和静脉单剂量注射15 mg＆#183;kg-1 QO-58,于给药后不同时间采集血样,乙腈沉淀蛋白,HPLC内标法测定血药浓度,DAS2.1.1软件计算药代动力学参数。结果血浆标准曲线在0．1~160 mg＆#183; L-1范围内线性良好。血浆中QO-58的最低定量限（ LQD ）为0．1 mg＆#183;L-1。方法回收率为89．56%~101．38%,精密度良好,日内和日间RSD中、高浓度样品均小于15%,低浓度样品小于20%。大鼠灌胃及注射给药,药时曲线均呈二室模型。 QO-58灌胃给药25、50、100 mg ＆#183; kg-1的主要药动学参数如下：Cmax （ mg＆#183;L-1）为8．25、16．29、18．27；T 12β（ h）：8．24、5．01、5．92；AUC0-∞（ g ＆#183; min ＆#183; L-1）：261．94、189．57、90．65。结论所建立的HPLC方法简单、专属性强,适用于QO-58在大鼠体内的药代动力学研究。Aim To develop a sensitive, specific and accurate method for the pharmacokinetic study of QO-58 （ a novel M channel opener ） in rats after intragas-tric （ ig） and intravenous （ iv） administration. Meth-ods QO-58 was administered at the doses of 25,50, 100 mg ·kg-1 （ ig ） and at single dose of 100 mg ＆#183; kg-1（iv）, respectively. Blood samples were obtained at intervals after each administration. Plasma samples were deproteinized with acetonitrile after addition of in-ternal standard, and detected by RP-HPLC. The main parameters of pharmacokinetics were calculated by DAS2. 1. 1 software. Results The calibration curve in plasma was linear over the range of 0. 1 ~160 mg ＆#183; L-1 in rat plasma, and the limit of detection （ LOD） was 0. 1 mg ＆#183; L-1 . The intra-day and inter-day RSD＆amp;nbsp;was less than 20%. The recovery of QO-58 in rat plas-ma was 89. 56% ~101. 38%. The concentration-time curves of QO-58 in rat palsma were consistent with the two-compartment model after both oral and intravenous administration. The main pharmacokinetic parameters for QO-58 following oral administration with three doses （25, 50, 100 mg·kg-1 ） in rat were as follows：Cmax （mg·L-1）：8.25,16.29,18.27;T12β（h）： 8.24, 5. 01, 5. 92; AUC0-∞ （ g· min · L-1 ）：261. 94, 189. 57,90. 65. Conclusion The developed method is simple and specific, and is suitable for preclinical pharmacokinetic studies of QO-58 .

关 键 词：QO-58 药代动力学 高效液相色谱法 大鼠 钾通道 灌胃 QO-58 

分 类 号：R332[医药卫生—人体生理学] R329.24[医药卫生—基础医学]