Albumin-Mediated Drug Uptake by Organic Anion Transporter 1/3 Is Real: Implications for the Prediction of Active Renal Secretion Clearance.

ABSTRACT: Modulation of the transport-mediated active uptake by human serum albumin (HSA) for highly protein-bound substrates has been reported and improved the in vitro-to-in vivo extrapolation (IVIVE) of hepatic clearance. However, evidence for the relevance of such a phenomenon in the case of renal transporters is sparse. In this study, transport of renal organic anion transporter 1 or 3 (OAT1/3) substrates into conditionally immortalized proximal tubular epithelial cells transduced with OAT1/3 was measured in the presence and absence of 1 and 4% HSA while keeping the unbound substrate concentration constant (based on measured fraction unbound, f_u,inc). In the presence of 4% HSA, the unbound intrinsic active uptake clearance (CL_int,u,active) of six highl

SUBMITTER: Tan SPF 

PROVIDER: S-EPMC11372837 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature