Gene names: Solute carrier organic anion transporter family member 1B1/1B3/2B1 (Slco1b1 / 1b3 / 2b1)
Animal models are important tools for estimating drug disposition and the probability of drug-drug interactions in humans. Among the preclinical species, monkeys are the closest to human in terms of pharmacokinetic/pharmacodynamic characteristics due to our evolutionary kinship. The use of cynomolgus monkey (Macaca fascicularis) has increased significantly in the past few years.
Organic anion-transporting polypeptides (OATP) 1B1, 1B3 and 2B1 are major uptake transporters that play an important role in drug disposition . The OATP family members are poorly conserved across more distantly related species such as humans, dogs and rodents . Cynomolgus monkey Oatps, however, show a high degree of amino acid sequence homology with their human orthologs. In the case of cyOatp1b1, cyOatp1b3 and cyOatp1b2 the identities are 91.9%, 93.5% and 96.6%, respectively [3, 4]. Cynomolgus Oatps are expressed exclusively in the liver , and show higher protein levels as compared with humans .
The substrate specificities and inhibition profiles of cyOatps are also similar to those of their human counterparts [3, 6], with some notable exceptions. Digoxin, for example, is a hOATP1B3-specific substrate , and whereas hOATP1B1, cyOatp1b1 and hOATP1B3 are most potently inhibited by rifampin, cyOatp1b3 is more sensitive to cyclosporin A than rifampin inhibition . Further, rifampin is less powerful at inhibiting cyOatp2b1-mediated rosuvastatin and atorvastatin uptake, but exhibits strong inhibition of cyOatp1b1- and cyOatp1b3-mediated rosuvastatin and atorvastatin uptake . Lack of translation of atorvastatin-rifampin DDI from cynomolgus monkeys to humans indicates species differences in the rate-limiting elimination pathways . In humans, hepatic and renal clearance of rosuvastatin are estimated to account for 72% and 28% of total elimination [8, 9], whereas the renal clearance was significantly lower (<5%)  in cynomolgus monkey.
Although further characterization of monkey transporters will be needed and differences in rate-limiting pathways betweeen monkeys and humans must be taken into consideration, these features suggest that cynomolgus monkeys may serve as a model for predicting OATP-mediated drug-drug interactions (DDIs) in humans .
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4. White, E.P., et al., Cloning and characterization of rhesus monkey and cynomolgus monkey organic anion transporting polypeptide 1b3, and comparison of their substrate selectivity with human OATP1B3. Drug Metab Rev, 2006. 38(Suppl 2): p. 232-3.
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9. Yoshida, K., K. Maeda, and Y. Sugiyama, Transporter-mediated drug--drug interactions involving OATP substrates: predictions based on in vitro inhibition studies. Clin Pharmacol Ther, 2012. 91(6): p. 1053-64.