2,3-吲哚醌在大鼠体内的药代动力学研究

目的考察单次静脉注射和口服给予大鼠2,3-吲哚醌后的药代动力学,为该药的新药开发提供依据。方法大鼠给药后经眼眶静脉采大约0.25 ml血液,采集时间点为：给予受试物前（0hr）和给予受试物后5 min,15min,30 min,1 h,2 h,4 h,6 h,8 h和24 h。血液样本采集后置于冰上,并立即取出50μl全血采用甲醇蛋白沉淀进行预处理,奎硫平作为内标。预处理后样品采用LC/MS/MS法进行测定,并用药动学处理软件WinNonlin 5.2采用非房室模型计算相关药代动力学参数。结果 Sprague Dawley大鼠静脉注射和口服两种制剂的药动学参数（平均值±标准偏差）如下。静脉注射：Tmax为0.83±0.29 hr,Cmax为141.53±10.99μg/L,T1/2为1.68±0.84 hr,AUC0-t为1068.15±389.06μg.hr/L,AUC0-∞为1211.19±469.18μg.hr/L,Vz为4.13±1.41 L/kg,CLz为1.89±0.94 L/hr/kg;口服：Tmax为0.05±0.00 hr,Cmax为1725.53±469.70 ng/ml,t 1/2为4.21±2.78 hr,AUC0-t为7711.21±2533.12μg.hr/L,AUC0-∞为7986.07±2623.38μg.hr/L,以AUC0-t计算,生物利用度平均为57.75±18.97%。结论 2,3-吲哚醌大鼠体内消除较快,可能存在非线性消除,口服吸收较好。

Pharmacokinetics of 2,3-indolinedione in rats

Objective:To study the pharmacokinetics of 2,3-indolinedione in rats after single administration of the drug orally or intravenously and to provide some information for the development of the new drug.Methods:0.25 ml blood were sampled from rats before and 5 min,15 min,30 min,1 h,2 h,4 h,6 h,8 h,24 h after drug administration.The blood samples were pretreated by protein precipitation method using methanol.Quetiapine was used as internal standard.After pretreatment,the samples were assayed by LC/MS/MS mothod...