依帕司他在C57BL/6J小鼠中的敏感性分析及药代动力学研究。
Sensitive analysis and pharmacokinetic study of epalrestat in C57BL/6J mice.
作者信息
Huang Jingqiu, Sun Runbin, Feng Siqi, He Jun, Fei Fei, Gao Haoxue, Zhao Yuqing, Zhang Yue, Gu Huilin, Aa Jiye, Wang Guangji
机构信息
State Key Laboratory of Natural Medicines, Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
出版信息
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jun 15;1055-1056:98-103. doi: 10.1016/j.jchromb.2017.03.040. Epub 2017 Apr 7.
Epalrestat is clinically applied for the management of diabetic peripheral neuropathy, yet its pharmacokinetic properties are not well understood. In this study, a rapid and sensitive LC-MS/MS method was established for assaying epalrestat in bio-samples of mice. The method was validated and it showed a good linearity over the range of 2-5000ng/mL, a precision of less than 12.3%, and recovery and matrix effects of 112.5-123.6% and 87.9-89.5%, respectively. After administration of a single dose of epalrestat administered, the exposure level of AUC was positively dose-dependent and the mean C, AUC, T, and MRT were 36.23±7.39μg/mL, 29,086.5μg/Lh, 1.2h and 1.8h, respectively. Epalrestat was highly exposed in stomach, intestine, liver and kidney, and only a small amount was detected in brain, urine and feces. Multi-dose of epalrestat significantly increased MRT and apparent volume of distribution (V) relative to those of a single-dose.
依帕司他临床上用于治疗糖尿病性周围神经病变，但其药代动力学特性尚未完全明确。本研究建立了一种快速灵敏的液相色谱-串联质谱法（LC-MS/MS），用于测定小鼠生物样品中的依帕司他。该方法经过验证，在2-5000ng/mL范围内线性良好，精密度小于12.3%，回收率和基质效应分别为112.5-123.6%和87.9-89.5%。单次给予依帕司他后，AUC的暴露水平呈正剂量依赖性，平均C、AUC、T和MRT分别为36.23±7.39μg/mL、29,086.5μg/Lh、1.2h和1.8h。依帕司他在胃、肠、肝和肾中暴露量高，在脑、尿液和粪便中仅检测到少量。与单次给药相比，多次给予依帕司他显著增加了MRT和表观分布容积（V）。
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