Simulation-Based Analysis of the Impact of Renal Impairment on the Pharmacokinetics of Highly Metabolized Compounds.

ABSTRACT: Renal impairment (RI) is a highly prevalent disease which can alter the pharmacokinetics (PK) of xenobiotics, including those that are predominately metabolized. The expression and activity of drug metabolizing enzymes (DMEs) and protein binding of compounds has been demonstrated to be affected in RI. A simulation based approach allows for the characterization of the impact of changes in these factors on the PK of compounds which are highly metabolized and allows for improved prediction of PK in RI. Simulations with physiologically based pharmacokinetic (PBPK) modeling was utilized to define the impact of these factors in PK in RI for a model substrate, nifedipine. Changes in fraction unbound and DME expression/activity had profound effects on PK in RI. Increasing fraction unbound and DME

SUBMITTER: Follman KE 

PROVIDER: S-EPMC6471170 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature