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Polypharmacy commonly exists in older and chronic disease populations. Transporters can interact with a wide range of endogenous and xenobiotic substrates. Significant drug–drug interactions (DDI) can lead to unfavorable efficacy and safety concerns, and therefore, industry, academia, and regulatory agencies have increased the recognition of transporter‐mediated drug interactions. In 2010, the ITC proposed seven transporters as sites for DDIs including P‐gp, BCRP, OATP1B1 and 1B3, OAT1 and 3, and OCT2 [37], which was updated to include MATEs. More recently, the ITC suggested that OCT1 and OATP2B1 be added [38]. The FDA cites manuscripts from the ITC recently published DDI guidance documents, including one focused on in vitro DDI assessment and the other focused on clinical DDI evaluation. These guidances describe the conduct of in vitro transporter studies and the use of specific criteria to assess the potential for drugs to interact with transporters and either perpetrate DDIs or be subjected to DDIs. More recently, potential endogenous biomarkers for transporters are being explored as an additional approach to assess the DDI liability of drug candidates [39]. For OCTs, potential biomarkers, which may lack specificity for individual OCT isoforms, include NMN, tryptophan, and creatinine in addition to thiamine [39]. Full assessment of the biosynthesis and elimination pathways of these compounds as well as extensive studies validating their specificity and usefulness in predicting clinical DDIs are needed.