Integrated Microphysiological Systems for Advanced ADME Modeling: From Absorption Routes to Multi-Organ Pharmacokinetics
DOI:
https://doi.org/10.18690/Keywords:
microphysiological systems, ADME, absorption, transdermal delivery, drug–drug interactionsAbstract
Despite significant advances in understanding diseases and developing new therapeutics, the translation of scientific knowledge into effective therapies remains slow and costly. A key challenge in drug development lies in the high failure rate during clinical phases, often due to the limited predictive value of preclinical models for absorption, distribution, metabolism, and excretion (ADME) properties. Traditional ADME assessment methods, including animal models and basic in vitro systems, show limited human relevance and face various limitations due to ethical, economic, and physiological considerations. The development of microphysiological systems (MPS), such as organ-on-a-chip platforms, offers a promising alternative by more accurately mimicking human tissues and organs. There is a growing need for broadly integrated platforms that simulate different absorption types related to all major application routes, including peroral (intestinal), dermal/transdermal, subcutaneous, and intravenous, while enabling functional coupling with metabolic (liver), distribution (vascular), and excretory (renal) systems. This review summarizes current trends and challenges in developing multi-organ models for MPS in ADME and drug–drug interaction studies.
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