FCCC LOGO Faculty Publications
Guo Y , Chu X , Parrott NJ , Brouwer KLR , Hsu V , Nagar S , Matsson P , Sharma P , Snoeys J , Sugiyama Y , Tatosian D , Unadkat JD , Huang SM , Galetin A
Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and PBPK Modeling Approaches
Clin Pharmacol Ther. 2018 Nov;104(5) :865-889
PMID: 30059145    PMCID: PMC6197917    URL: https://www.ncbi.nlm.nih.gov/pubmed/30059145
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This white paper examines recent progress, applications and challenges in predicting unbound and total tissue and intra/subcellular drug concentrations using in vitro and preclinical models, imaging techniques and physiologically-based pharmacokinetic (PBPK) modeling. Published examples, regulatory submissions and case studies illustrate the application of different types of data in drug development to support modeling and decision making for compounds with transporter-mediated disposition, and likely disconnects between tissue and systemic drug exposure. The goals of this manuscript are to illustrate current best practices and outline practical strategies for selecting appropriate in vitro and in vivo experimental methods to estimate or predict tissue and plasma concentrations, and to use these data in the application of PBPK modeling for human PK, efficacy and safety assessment in drug development. This article is protected by copyright. All rights reserved.
1532-6535 Guo, Yingying Chu, Xiaoyan Parrott, Neil J Brouwer, Kim L R Hsu, Vicky Nagar, Swati Matsson, Par Sharma, Pradeep Snoeys, Jan Sugiyama, Yuichi Tatosian, Daniel Unadkat, Jashvant D Huang, Shiew-Mei Galetin, Aleksandra International Transporter Consortium Journal Article United States Clin Pharmacol Ther. 2018 Jul 30. doi: 10.1002/cpt.1183.