Abstract

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 used 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. 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 enable an early in vitro-to-in vivo extrapolation 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.