RT Journal Article SR Electronic T1 Cynomolgus Monkey as an Emerging Animal Model to Study Drug Transporters: In Vitro, In Vivo, In Vitro-To-In Vivo Translation JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP DMD-MR-2021-000695 DO 10.1124/dmd.121.000695 A1 Hong Shen A1 Zheng Yang A1 A. David Rodrigues YR 2021 UL http://dmd.aspetjournals.org/content/early/2021/12/10/dmd.121.000695.abstract AB Membrane transporters have been recognized as one of the key determinants of pharmacokinetics and are also known to affect the efficacy and toxicity of drugs. Both qualitatively and quantitatively, however, transporter studies conducted using human in vitro systems have not always been predictive. Consequently, researchers have utilized cynomolgus monkeys as a model to study drug transporters and anticipate their effects in humans. Burgeoning reports of data in the last few years necessitates a comprehensive review on the topic of drug transporters in cynomolgus monkeys that includes cell-based tools, sequence homology, tissue expression, in vitro studies, in vivo studies, and in vitro-to-in vivo extrapolation (IVIVE). This review highlights the state-of-the-art applications of monkey transporter models to support the evaluation of transporter-mediated drug-drug interactions, clearance predictions, and endogenous transporter biomarker identification and validation. The data demonstrate that cynomolgus monkey transporter models, when used appropriately, can be an invaluable tool to support drug discovery and development processes. Most importantly, they provide an early IVIVE assessment which provides additional context to human in vitro data. Additionally, comprehending species similarities and differences in transporter tissue expression and activity is crucial when translating monkey data to humans. The challenges and limitations when applying such models to inform decision-making must also be considered. Significance Statement This paper presents a comprehensive review of currently available published reports describing cynomolgus monkey transporter models. The data indicate that cynomolgus monkeys provide mechanistic insight regarding the role of intestinal, hepatic, and renal transporters in drug and biomarker disposition and drug interactions. It is concluded that the data generated with cynomolgus monkey models provide mechanistic insight regarding transporter-mediated absorption and disposition, as well as human clearance prediction, drug-drug interaction assessment, and endogenous biomarker development related to drug transporters.