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Interspecies scaling: prediction of human biliary clearance and comparison with QSPKR
Author(s) -
Morris Marilyn E.,
Yang Xinning,
Gandhi Yash A.,
Bhansali Suraj G.,
Benincosa Lisa J.
Publication year - 2012
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.1761
Subject(s) - metabolic clearance rate , scaling , pharmacokinetics , medicine , mathematics , computational biology , pharmacology , biology , geometry
The aim of this study was to evaluate the prediction performance of various allometric scaling methods in predicting human biliary clearance ( CL b ) from data in rats or multiple animal species and to compare the prediction performance with that of quantitative structure pharmacokinetic relationship (QSPKR) models. CL b data of parent drugs in rats and humans were collected from the literature for 18 compounds. A simple allometric approach was applied to CL b or unbound CL b using 0.75 or 0.66 as the allometric exponent. For scaling from rat studies alone, the prediction using 0.66 as the exponent was better than that using 0.75, and a better prediction was obtained for unbound CL b than CL b . For a subset of compounds, six multiple‐species scaling methods were compared, with the best prediction achieved with the simple unbound CL b approach. However, in the absence of protein binding data, the correction with maximum life‐span potential (MLP) or ‘Rule of exponent’ (ROE) method offered the best prediction. Overall, multiple species had better predictability than scaling with the rat alone. Comparison of predicted human CL b values using multiple animal species and QSPKR offered similar prediction performance. In conclusion, the results of the present study, although based on limited data, suggested that the prediction for human CL b by allometry was greatly improved by the incorporation of protein binding. Human CL b prediction using rat data alone was not satisfactory. Additionally, QSPKR provides an alternative approach to allometry for the prediction of human biliary clearance. Copyright © 2011 John Wiley & Sons, Ltd.