Effect of Chronic Kidney Disease on the Renal Secretion via Organic Anion Transporters 1/3: Implications for Physiologically-Based Pharmacokinetic Modeling and Dose Adjustment.

ABSTRACT: There is growing evidence that active tubular secretory clearance (CL_s ) may not decline proportionally with the glomerular filtration rate (GFR) in chronic kidney disease (CKD), leading to the overestimation of renal clearance (CL_r ) when using solely GFR to approximate disease effect on renal elimination. The clinical pharmacokinetic data of 33 renally secreted OAT1/3 substrates were collated to investigate the impact of mild, moderate, and severe CKD on CL_r , tubular secretion and protein binding (f_u,p ). The f_u,p of the collated substrates ranged from 0.0026 to 1.0 in healthy populations; observed CKD-related increase in the f_u,p (up to 2.7-fold) of 8 highly bound substrates (f_u,p  ≤ 0.2) was accounted for in

SUBMITTER: Tan SPF 

PROVIDER: S-EPMC9540491 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature