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ADMET and DMPK, Vol.4 No.1 March 2016. -

Biologics mainly monoclonal antibodies mAbs and antibody-drug conjugates ADCs as new therapeutics are becoming increasingly important biotherapeutics. This review is intended to provide an overall comparison between small molecules SMs and biologics or large molecules LMs concerning drug metabolism and pharmacokinetic DMPK or associated with absorption, distribution, metabolism and elimination ADME testing from pharmaceutical industry drug discovery and development points of view, which will help design and conduct relevant ADME testing for biologics such as mAbs and ADCs. Recent advancements in the ADME for testing biologics and related bioanalytical methods are discussed with an emphasis on ADC drug development as an example to understand its complexity and challenges from extensive in vitro characterization to in vivo animal PK studies. General non-clinical safety evaluations of biologics in particular for ADC drugs are outlined including drug-drug interaction DDI and metabolite-catabolite assessments. Regulatory guidance on the ADME testing and safety evaluations including immunogenicity as well as bioanalytical considerations are addressed for LMs. In addition, the preclinical and human PK data of two marked ADC drugs ADCETRIS, SGN-35 and KADCYLA, T-DM1 as examples are briefly discussed with regard to PK considerations and PK-PD perspectives.

monoclonal antibody; antibody-drug conjugate; pharmacokinetics; bioanalysis; preclinical safety



Autor: Hong Wan - ; Shanghai Hengrui Pharmaceutical Co., LTD. Dept. of DMPK-Tox, Shanghai, P.R. China

Fuente: http://hrcak.srce.hr/



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