Design and application of microfluidic systems for in vitro pharmacokinetic evaluation of drug candidates

T. J. Maguire, E. Novik, P. Chao, J. Barminko, Y. Nahmias, M. L. Yarmush, K. C. Cheng*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations

Abstract

One of the fundamental challenges facing the development of new chemical entities within the pharmaceutical industry is the extrapolation of key in vivo parameters from in vitro cell culture assays and animal studies. Development of microscale devices and screening assays incorporating primary human cells can potentially provide better, faster and more efficient prediction of in vivo toxicity and clinical drug performance. With this goal in mind, large strides have been made in the area of microfluidics to provide in vitro surrogates that are designed to mimic the physiological architecture and dynamics. More recent advancements have been made in the development of in vitro analogues to physiologically-based pharmacokinetic (PBPK) models - a mathematical model that represents the body as interconnected compartments specific for a particular organ. In this review we highlight recent advancements in human hepatocyte microscale culture, and describe the next generation of integrated devices, whose potential allows for the high throughput assessment of drug metabolism, distribution and pharmacokinetics.

Original languageAmerican English
Pages (from-to)1192-1199
Number of pages8
JournalCurrent Drug Metabolism
Volume10
Issue number10
DOIs
StatePublished - Dec 2009

Keywords

  • Bioreactor
  • Coculture
  • Human hepatocyte
  • Microfluidics

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