P038: Impact of homocystinuria on the brain and nervous system

0.054 M) and dT (0.112 M) at the highest anticipated daily dose.Potential in vivo inhibition of P-gp, BCRP and OATP1B1/B3 was further evaluated using I gut /IC 50 cut-off criteria (FDA 2020).Estimated I gut /IC 50 ratios were below the cut-off values for all 4 transporters, suggesting in vivo inhibition is unlikely.Doxecitine and doxribtimine was not a substrate for P-gp, OAT1, OAT3 or OCT2.dC was unlikely to be a substrate of BCRP, whereas dT was considered a possible substrate of BCRP.Fumitremorgin C, a reference BCRP inhibitor, had minimal or no effect on bidirectional efflux of dT (1 M and 10 M), indicating BCRP has a minor role, if any, in dT transport at these concentrations.Conclusion: Clinically relevant concentrations of doxecitine and doxribtimine are unlikely to cause or be subject to pharmacokinetic DDIs mediated by plasma protein binding displacement, CYP-mediated metabolism or activity at common drug transporters.