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Annual Review of Pharmacology and Toxicology

Volume 58, 2018

Physiologically Based Pharmacokinetic and Pharmacodynamic Analysis Enabled by Microfluidically Linked Organs-on-Chips

Abstract

Physiologically based pharmacokinetic (PBPK) modeling and simulation approaches are beginning to be integrated into drug development and approval processes because they enable key pharmacokinetic (PK) parameters to be predicted from in vitro data. However, these approaches are hampered by many limitations, including an inability to incorporate organ-specific differentials in drug clearance, distribution, and absorption that result from differences in cell uptake, transport, and metabolism. Moreover, such approaches are generally unable to provide insight into pharmacodynamic (PD) parameters. Recent development of microfluidic Organ-on-a-Chip (Organ Chip) cell culture devices that recapitulate tissue-tissue interfaces, vascular perfusion, and organ-level functionality offer the ability to overcome these limitations when multiple Organ Chips are linked via their endothelium-lined vascular channels. Here, we discuss successes and challenges in the use of existing culture models and vascularized Organ Chips for PBPK and PD modeling of human drug responses, as well as in vitro to in vivo extrapolation (IVIVE) of these results, and how these approaches might advance drug development and regulatory review processes in the future.

Keyword(s): drug development, IVIVE, microfluidic, microphysiological system, organ-on-a-chip, pharmacodynamics, pharmacokinetics
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/content/journals/10.1146/annurev-pharmtox-010716-104748
2018-01-06
2024-04-19
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Physiologically Based Pharmacokinetic and Pharmacodynamic Analysis Enabled by Microfluidically Linked Organs-on-Chips
Annual Review of Pharmacology and Toxicology 58, 37 (2018); https://doi.org/10.1146/annurev-pharmtox-010716-104748
/content/journals/10.1146/annurev-pharmtox-010716-104748
/content/journals/10.1146/annurev-pharmtox-010716-104748
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  • Article Type: Review Article

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