Prediction of human drug clearance using a single-species, fixed-exponent allometric approach

Teh M. Hu, Shih Jiuan Chiu

研究成果: 雜誌貢獻文章

4 引文 斯高帕斯(Scopus)

摘要

Background: Human pharmacokinetics can be predicted from animal data using the principle of allometry, which assumes a mathematical power-law relationship between pharmacokinetic parameters and body weights of animal species. The objective of the present study was to investigate the feasibility of extrapolating human drug clearance (CL) from a single animal species using simple allometry with a fixed body-weight exponent. Methods: CL values from rat, monkey, dog and human for 109 compounds were obtained from the literature. A normalization procedure based on the concept of a characteristic CL value was first introduced to homogenize and pool the CL data for a regression analysis. The allometric exponent from the regression analysis was then used as the exponent for CL extrapolation. The prediction performance of the proposed method was compared with methods that incorporate liver blood flow (LBF) or maximum life-span potential (MLP). Results: An allometric exponent of 0.67 (95% CI, 0.64 to 0.71) adequately described the pooled CL data. A fixed value of 0.67 as the body-weight scaling exponent and monkey CL provided the best estimate of human CL, followed by rat and dog. CL prediction by the LBF approach was comparable to that of the fixed-exponent method. The MLP approach systematically underestimated the human CL. Conclusions: It is feasible to predict human drug CL from CL measured in a single animal species using simple allometry with a fixed body-weight exponent of 0.67. While monkey provides the best estimate of human CL, rat, but not dog, offers an acceptable prediction when monkey data are unavailable.

原文英語
頁(從 - 到)331-339
頁數9
期刊Journal of Medical Sciences (Taiwan)
29
發行號6
出版狀態已發佈 - 十二月 2009

ASJC Scopus subject areas

  • Medicine(all)

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