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Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Biol Chem. Apr 26, 2012; 3(4): 73-92
Published online Apr 26, 2012. doi: 10.4331/wjbc.v3.i4.73
Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges
Yulia Vugmeyster, Xin Xu, Frank-Peter Theil, Leslie A Khawli, Michael W Leach
Yulia Vugmeyster, Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., Andover, MA 01810, United States
Xin Xu, Center for Translational Therapeutics, National Institutes of Health, Rockville, MD 20850, United States
Frank-Peter Theil, UCB Pharma, Braine l’Aleud, B-1420 Brussels, Belgium
Leslie A Khawli, Pharmacokinetic and Pharmacodynamic Sciences, Genentech Inc., South San Francisco, CA 94080, United States
Michael W Leach, Drug Safety Research and Development, Pfizer Inc., Andover, MA 01810, United States
Author contributions: Vugmeyster Y, Leach MW, and Xu X conceived and wrote this review; Theil FP and Khawli LA contributed to the conception of this review and critically reviewed the manuscript.
Correspondence to: Yulia Vugmeyster, PhD, Senior Principal Scientist, Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., Andover, MA 01810, United States. yulia.vugmeyster@pfizer.com
Telephone: +1-978-2471404 Fax: +1-978-2472842
Received: November 10, 2011
Revised: January 18, 2012
Accepted: January 25, 2012
Published online: April 26, 2012
Abstract

Significant progress has been made in understanding pharmacokinetics (PK), pharmacodynamics (PD), as well as toxicity profiles of therapeutic proteins in animals and humans, which have been in commercial development for more than three decades. However, in the PK arena, many fundamental questions remain to be resolved. Investigative and bioanalytical tools need to be established to improve the translation of PK data from animals to humans, and from in vitro assays to in vivo readouts, which would ultimately lead to a higher success rate in drug development. In toxicology, it is known, in general, what studies are needed to safely develop therapeutic proteins, and what studies do not provide relevant information. One of the major complicating factors in nonclinical and clinical programs for therapeutic proteins is the impact of immunogenicity. In this review, we will highlight the emerging science and technology, as well as the challenges around the pharmacokinetic- and safety-related issues in drug development of mAbs and other therapeutic proteins.

Keywords: Pharmacokinetics; Toxicology; Therapeutic proteins; Biotherapeutics; Monoclonal antibodies