A novel model for prediction of human drug clearance by allometric scaling

Huadong Tang; Michael Mayersohn

doi:10.1124/dmd.105.004143

A novel model for prediction of human drug clearance by allometric scaling

Huadong Tang, Michael Mayersohn

Pharmacy Practice and Science

Research output: Contribution to journal › Article › peer-review

130 Scopus citations

Abstract

Sixty-one sets of clearance (CL) values in animal species were allometrically scaled for predicting human clearance. Unbound fractions (f _u) of drug in plasma in rats and humans were obtained from the literature. A model was developed to predict human CL: CL = 33.35 ml/min x (a/Rf_u)^0.770, where Rf_u is the f_u ratio between rats and humans and a is the coefficient obtained from allometric scaling. The new model was compared with simple allometric scaling and the "rule of exponents" (ROE). Results indicated that the new model provided better predictability for human values of CL than did ROE. It is especially significant that for the first time the proposed model improves the prediction of CL for drugs illustrating large vertical allometry.

Original language	English (US)
Pages (from-to)	1297-1303
Number of pages	7
Journal	Drug Metabolism and Disposition
Volume	33
Issue number	9
DOIs	https://doi.org/10.1124/dmd.105.004143
State	Published - Sep 2005

ASJC Scopus subject areas

Pharmacology
Pharmaceutical Science

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abstract = "Sixty-one sets of clearance (CL) values in animal species were allometrically scaled for predicting human clearance. Unbound fractions (f u) of drug in plasma in rats and humans were obtained from the literature. A model was developed to predict human CL: CL = 33.35 ml/min x (a/Rfu)0.770, where Rfu is the fu ratio between rats and humans and a is the coefficient obtained from allometric scaling. The new model was compared with simple allometric scaling and the {"}rule of exponents{"} (ROE). Results indicated that the new model provided better predictability for human values of CL than did ROE. It is especially significant that for the first time the proposed model improves the prediction of CL for drugs illustrating large vertical allometry.",

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AB - Sixty-one sets of clearance (CL) values in animal species were allometrically scaled for predicting human clearance. Unbound fractions (f u) of drug in plasma in rats and humans were obtained from the literature. A model was developed to predict human CL: CL = 33.35 ml/min x (a/Rfu)0.770, where Rfu is the fu ratio between rats and humans and a is the coefficient obtained from allometric scaling. The new model was compared with simple allometric scaling and the "rule of exponents" (ROE). Results indicated that the new model provided better predictability for human values of CL than did ROE. It is especially significant that for the first time the proposed model improves the prediction of CL for drugs illustrating large vertical allometry.

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A novel model for prediction of human drug clearance by allometric scaling

Abstract

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