Metabolite to parent drug concentration ratio as a function of parent drug extraction ratio: Cases of nonportal route of administration

Abstract

The ratio of metabolite to parent drug concentration (Cm/Cp)of a medium or high extraction ratio (E>0.1)drug administered intravenously has been shown to depend on intrinsic clearance of drug by other metabolic routes (CL_r,int)as well as on organ blood flow (Q).In contrast, for a low extraction ratio drug given intravenously or for any drug given by a portal route, this ratio is equal to the ratio of formation clearance (CL_f,int)and metabolite clearance (CL_m,int).The sensitivity of Cm/Cpto changes in CL_r,intand CL_f,inthas been analyzed quantitatively. It was shown to be dependent on the fraction metabolized to that particular metabolite (fm).