Novel minimal physiologically-based model for the prediction of passive tubular reabsorption and renal excretion clearance.

ABSTRACT:

Purpose

Develop a minimal mechanistic model based on in vitro-in vivo extrapolation (IVIVE) principles to predict extent of passive tubular reabsorption. Assess the ability of the model developed to predict extent of passive tubular reabsorption (F_reab) and renal excretion clearance (CL_R) from in vitro permeability data and tubular physiological parameters.

Methods

Model system parameters were informed by physiological data collated following extensive literature analysis. A database of clinical CL_R was collated for 157 drugs. A subset of 45 drugs was selected for model validation; for those, Caco-2 permeability (P_app) data were measured under pH6.5-7.4 gradient conditions and used to predict F_reab and subsequently CL

SUBMITTER: Scotcher D 

PROVIDER: S-EPMC5074076 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature