Pharmacokinetics and toxicology of therapeutic proteins:Advances and challenges  

作　　者：Yulia Vugmeyster Frank-Peter Theil Leslie A Khawli Michael W Leach 

机构地区：[1]Department of Pharmacokinetics,Dynamics,and Metabolism,Pfizer Inc.,Andover,MA 01810,United States [2]UCB Pharma,Braine l'Aleud,B-1420 Brussels,Belgium [3]Pharmacokinetic and Pharmacodynamic Sciences,Genentech Inc.,South San Francisco,CA 94080,United States [4]Drug Safety Research and Development,Pfizer Inc.,Andover,MA 01810,United States

出　　处：《World Journal of Biological Chemistry》2012年第4期73-92,共20页世界生物化学杂志（英文版）（电子版）

摘　　要：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.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.

关 键 词：PHARMACOKINETICS TOXICOLOGY Therapeutic proteins BIOTHERAPEUTICS MONOCLONAL ANTIBODIES 

分 类 号：R96[医药卫生—药理学]