Multi-organ-on-a-chip for pharmacokinetics and toxicokinetic study of drugs

ABSTRACT

Introduction: Accurate prediction of pharmacokinetic (PK) and toxicokinetics (TK) of drugs is imperative for successful development of new pharmaceutics. Although conventional in vitro methods for predicting the PK and TK of drugs are well established, limitations still exist and more advanced chip-based in vitro platforms combined with mathematical models can help researchers overcome the limitations. Areas covered: We will review recent progress in the development of multi-organ-on-a-chip platforms for predicting PK and TK of drugs, as well as mathematical approaches that can be combined with these platforms for experiment design, data analysis and in vitro-in vivo extrapolation (IVIVE) for application to humans. Expert opinion: Although there remain some challenges to be addressed, the remarkable progress in the area of multi-organ-on-a-chip in recent years indicate that we will see tangible outcomes that can be utilized in the pharmaceutical industry in near future.

KEYWORDS:

• Multi-organ-on-a-chip
• pbpk model
• pharmacodynamic
• pharmacokinetic
• toxicokinetic

Article highlights

• Organ-on-a-chip systems have successfully demonstrated that recreation of tissue microenvironment for cells can enhance the physiological relevance of cultured cells.

• Multi-organ-on-a-chip systems allow recapitulation of key interactions between different organs in the body, in the context of disease progression or whole-body response to drugs.

• How to correctly scale and design multi-organ systems is the key challenge in developing physiologically-realistic mimic of the human body.

• Mathematical modeling methods such as PK-PD models and quantitative pharmacology models are useful for designing and interpreting multi-organ-chip systems.

• Validation of organ-on-a-chip systems for their representation of human physiology and development of user-friendly devices are the key steps toward commercialization and wider acceptance in the pharmaceutical industry.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by National Research Foundation of Korea, under Grant (Basic Research Lab, 2019R1A4A1025958), and by the Ministry of Trade, Industry & Energy (MOTIE), Republic of Korea, under the Technology Innovation Program, Grant 20008414 (Development of intestine-liver-kidney multiorgan tissue chip mimicking absorption distribution metabolism excretion of drug), and by the Hongik University Research Fund.