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小鼠的毛细血管微量采样:在药代动力学分析中从稀疏采样转向连续采样的有效方法。

Capillary microsampling in mice: effective way to move from sparse sampling to serial sampling in pharmacokinetics profiling.

作者信息

Raje Amol A, Mahajan Vallabh, Pathade Vishal V, Joshi Kaushal, Gavali Ashutosh, Gaur Ashwani, Kandikere Vishwottam

机构信息

Drug Metabolism Pharmacokinetics and Clinical Pharmacology, Eurofins Advinus Ltd., (Formerly known as Advinus Therapeutics Ltd), Bengaluru, India.

出版信息

Xenobiotica. 2020 Jun;50(6):663-669. doi: 10.1080/00498254.2019.1683259. Epub 2019 Oct 30.

Abstract

Pharmacokinetic studies are an integral part of drug discovery and development. Mice are the commonly used species for pharmacokinetics studies during early discovery studies. Conventionally, composite PK profiles are obtained from mice studies due to the physiological limitations of the total blood volume that can be drawn over a certain period.With advancements in bioanalytical instrumentation and in blood sampling techniques, analysis with small volume (<50 µL) became feasible enabling serial blood sampling from the mouse for PK studies. The objective of the current study was to develop and establish a serial blood sampling technique in mouse and compare it with the conventional sparse sampling method (composite PK) following oral administration of widely used NSAIDs, diclofenac, celecoxib and tenoxicam, into Swiss Albino mice.The pharmacokinetic parameters of all three probe drugs by serial blood sampling were comparable with that of sparse sampling method. There was no significant difference between the whole blood concentration time profiles of all three drugs between serial sampling and sparse sampling suggesting serial blood sampling method can be easily implemented for mice PK studies.Serial blood sampling technique requires use of fewer number of animals, less quantity of test compound and reduces the possible dosing errors as fewer number of animals need to be dosed resulting in quality PK data and enabling comparison of inter-animal differences in PK profile.

摘要

药代动力学研究是药物发现与开发不可或缺的一部分。在早期发现研究阶段,小鼠是药代动力学研究中常用的物种。传统上,由于在一定时期内可采集的全血体积存在生理限制,小鼠研究只能获得综合药代动力学曲线。随着生物分析仪器和采血技术的进步,小体积(<50µL)分析变得可行,从而能够从小鼠身上进行连续采血以开展药代动力学研究。本研究的目的是开发并建立一种小鼠连续采血技术,并将其与传统的稀疏采样方法(综合药代动力学)进行比较,该传统方法是在给瑞士白化小鼠口服广泛使用的非甾体抗炎药双氯芬酸、塞来昔布和替诺昔康后进行的。通过连续采血得到的所有三种受试药物的药代动力学参数与稀疏采样方法的参数相当。连续采样和稀疏采样时,所有三种药物的全血浓度-时间曲线之间没有显著差异,这表明连续采血方法可轻松用于小鼠药代动力学研究。连续采血技术需要使用的动物数量更少、受试化合物的用量更少,并且由于需要给药的动物数量较少,减少了可能的给药误差,从而产生高质量的药代动力学数据,并能够比较动物间药代动力学曲线的差异。

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