TABLE 1

The major advantages, disadvantages, and challenges of using cynomolgus monkey transporter models in support of drug transporter research

PropertyAdvantages and Limitations of Monkey Transporter Models
AdvantagesGeneticsShare ideal identity with greater than 90 percent of the DNA sequences of human drug transport systems that other mammalian species may lack [e.g., SLCO1B1 (OATP1B1 gene) and SLC47A2 (MATE2-K gene)]
Transport characteristicsMonkey is most similar to human with respect to substrate specificity, transport kinetics, and transporter inhibition potency
Pharmacokinetic investigationDisplay similar physiology and biochemistry properties compared with humans and have larger body size than rodent experimental models, making them suitable for pharmacokinetics disposition and drug interaction investigations
Transporter regulationShare greater similarities with humans in nuclear receptor functional regulation associated with transporters and drug-metabolizing enzymes (e.g., rifampin induction)
Translational sciencesRecapture numerous clinical transporter DDIs, and enable translation of vitro and animal data to clinical findings and confirming transport mechanism
Disadvantages/ChallengesTransporter expression and activitiesThere are likely species-dependent difference in transporter expression, transport kinetics, and substrate specificity between cynomolgus monkey and human
In vitro monkey transporter reagentsIn vitro transfected cell and membrane vesicle models are not widely available
Genetic background and variationThere are likely differences in some transporter gene sequences that have been encountered within cynomolgus monkeys sourced from different geographic origins (e.g., China, the Philippines, and Mauritius)