Novel Mechanistic PBPK Model to Predict Renal Clearance in Varying Stages of CKD by Incorporating Tubular Adaptation and Dynamic Passive Reabsorption.

ABSTRACT: Chronic kidney disease (CKD) has significant effects on renal clearance (CL_r ) of drugs. Physiologically-based pharmacokinetic (PBPK) models have been used to predict CKD effects on transporter-mediated renal active secretion and CL_r for hydrophilic nonpermeable compounds. However, no studies have shown systematic PBPK modeling of renal passive reabsorption or CL_r for hydrophobic permeable drugs in CKD. The goal of this study was to expand our previously developed and verified mechanistic kidney model to develop a universal model to predict changes in CL_r in CKD for permeable and nonpermeable drugs that accounts for the dramatic nonlinear effect of CKD on renal passive reabsorption of permeable drugs. The developed model incorporates physiologica

SUBMITTER: Huang W 

PROVIDER: S-EPMC7577018 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature