Projecting human pharmacokinetics of monoclonal antibodies from nonclinical data: comparative evaluation of prediction approaches in early drug development

This article presents a brief overview of the biology and mechanisms of absorption, distribution, metabolism and excretion (ADME) for mAbs. Additionally, we provide a detailed review of mAb human PK/PD prediction from nonclinical data, including allometry for mAbs with linear or nonlinear PK, species‐invariant time method, physiologically based PK (PBPK) modeling and target‐mediated drug disposition (TMDD) model, bioavailability projection and immunogenicity impact on PK prediction. Finally, from an industry perspective a decision tree of mAb human PK projection is proposed to facilitate drug development. This article is protected by copyright. All rights reserved.

Source: Biopharmaceutics and Drug Disposition - April 13, 2015 Category: Drugs & Pharmacology Authors: Jing Wang, Suhasini Iyer, Paul J. Fielder, John D. Davis, Rong Deng Tags: Invited Review Source Type: research