Format

Send to

Choose Destination
See comment in PubMed Commons below
Biopharm Drug Dispos. 2010 May;31(4):253-63. doi: 10.1002/bdd.708.

Prediction of human clearance of therapeutic proteins: simple allometric scaling method revisited.

Author information

1
Department of Drug Metabolism and Pharmacokinetics, Merck Research Laboratories, Merck Sharp & Dohme Corp., West Point, PA 19486, USA. weirong_wang@merck.com

Abstract

In this report, the utility of a commonly used interspecies scaling method to predict the systemic clearance (CL) of therapeutic proteins in humans was evaluated. Based on analysis of a pharmacokinetic data set of 34 therapeutic proteins, including 12 monoclonal antibodies (mAbs) and Fc fusion proteins, human CL can generally be predicted reasonably well with simple allometric scaling and a fixed exponent of 0.8: approximately 95% of the cases predicted values within 2-fold of the observed values when using CL data from multiple species, or approximately 90% simply using CL from monkeys. Specific to mAbs/Fc fusion proteins, scaling from monkey CL using a fixed exponent of 0.8 gave an excellent prediction; all predicted CL values were within 2-fold of the corresponding observed values. Compared with the simple allometric scaling method that uses a fitted exponent from CL data of > or =3 preclinical species, the fixed exponent approach with 1-2 preclinical species is simple, resource-saving and minimizes systematic bias. Together with its overall satisfactory prediction accuracy, especially in the absence of non-linear pharmacokinetics and species-specific clearance mechanisms, this fixed exponent method affords a viable alternative to other published allometric methods, including the Rule of Exponents (ROE).

PMID:
20437464
DOI:
10.1002/bdd.708
[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center