Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
Regular Article
Prediction of Human Pharmacokinetics of Therapeutic Monoclonal Antibodies from Simple Allometry of Monkey Data
Masataka OITATENoriko MASUBUCHITakashi ITOYoshiyuki YABETsuyoshi KARIBETakanori AOKINobuyuki MURAYAMAAtsushi KURIHARANoriko OKUDAIRATakashi IZUMI
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Supplementary material

2011 Volume 26 Issue 4 Pages 423-430

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Abstract

  Interspecies allometric scaling is a useful tool for calculating human pharmacokinetic (PK) parameters from data in animals. In this study, in order to determine the scaling exponent in a simple allometric equation that can predict human clearance (CL) and distribution volume at steady state (Vss) of monoclonal antibodies (mAbs) from monkey data alone, PK data of 24 mAbs were collected and analyzed according to the types of targeted antigens (soluble or membrane-bound antigens). Based on the observed PK data in humans (at clinical doses) and monkeys (at >1 mg/kg), where the PK is expected to be linear, the mean scaling exponents in the allometric equation for CL and Vss, respectively, against body weight were calculated to be 0.79 and 1.12 [95% confidence intervals (CIs): 0.69–0.89 and 0.96–1.28] for soluble antigens, and 0.96 and 1.00 (95% CIs: 0.83–1.09 and 0.87–1.13) for membrane-bound antigens. Using these exponents and monkey PK data (at >1 mg/kg) alone, both human CL and Vss of mAbs can be predicted with reasonable accuracy, i.e., within 2-fold of the observed values. Compared with traditional allometric scaling using PK data from three or more preclinical species, this approach is simple, quick, resource-saving, and useful in drug discovery and development.

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© 2011 by The Japanese Society for the Study of Xenobiotics
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