Advancing Predictions of Tissue and Intracellular Drug Concentrations Using In Vitro, Imaging and Physiologically Based Pharmacokinetic Modeling Approaches

Research output: Contribution to journalArticle

  • External authors:
  • Yingying Guo
  • Xiaoyan Chu
  • Neil J. Parrott
  • Kim L.r. Brouwer
  • Vicky Hsu
  • Swati Nagar
  • Pär Matsson
  • Pradeep Sharma
  • Jan Snoeys
  • Yuichi Sugiyama
  • Daniel Tatosian
  • Jashvant D. Unadkat
  • Shiew-mei Huang


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 article 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 pharmacokinetic (PK), efficacy, and safety assessment in drug development.

Bibliographical metadata

Original languageEnglish
Pages (from-to)865-889
JournalClinical Pharmacology & Therapeutics
Issue number5
Early online date30 Jul 2018
Publication statusPublished - 22 Oct 2018