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种间预测药代动力学参数的比例缩放原理的应用。

The application of allometric scaling principles to predict pharmacokinetic parameters across species.

机构信息

Institute of Computational Comparative Medicine, Kansas State University , Manhattan, KS 66506 , USA

出版信息

Expert Opin Drug Metab Toxicol. 2014 Sep;10(9):1241-53. doi: 10.1517/17425255.2014.934671. Epub 2014 Jul 2.

Abstract

INTRODUCTION

Interspecies allometric scaling provides a simple and fast option to interpolate or extrapolate drug dose or pharmacokinetic parameters to a species of interest. Over the years, new scaling methods have been developed in order to improve the performance of these predictions. It is critical to choose appropriate allometric scaling approach(es) to analyze the available pharmacokinetic data.

AREAS COVERED

This review provides updated information on the latest allometric scaling methods developed for the most frequently interpolated or extrapolated pharmacokinetic parameters. The different degrees of success and advantages/disadvantages of different methods are compared and contrasted. The pitfalls that affect the accuracy of prediction and the solutions to avoid the risk of prediction errors are discussed. The application of allometric scaling in veterinary medicine is presented.

EXPERT OPINION

Although interspecies allometric scaling needs further refinements and has limitations, it is still a potential tool and rational option for the estimate of pharmacokinetic parameters in species for which there are no data available or to better interpret preclinical efficacy and safety trials. Allometric scaling can offer insight into possible mechanisms of species-dependent drug disposition.

摘要

简介

种间比例缩放为药物剂量或药代动力学参数在感兴趣的物种间内插或外推提供了一种简单快捷的选择。多年来,为了提高这些预测的性能,已经开发了新的缩放方法。选择合适的比例缩放方法来分析现有的药代动力学数据至关重要。

涵盖领域

本文综述了最新的比例缩放方法,这些方法是为最常内插或外推的药代动力学参数而开发的。比较和对比了不同方法的不同程度的成功和优缺点。讨论了影响预测准确性的陷阱以及避免预测错误风险的解决方案。介绍了比例缩放在兽医医学中的应用。

专家意见

尽管种间比例缩放需要进一步改进并且存在局限性,但它仍然是一种潜在的工具和合理的选择,可以用于估计没有可用数据的物种的药代动力学参数,或者更好地解释临床前疗效和安全性试验。比例缩放可以深入了解与物种依赖性药物处置相关的可能机制。

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