Impact of ignoring extraction ratio when predicting drug-drug interactions, fraction metabolized, and intestinal first-pass contribution.

ABSTRACT: Many mathematical models for in vitro to in vivo prediction of drug-drug interactions (DDIs) of orally administered victim drugs have been developed. However, to date, none of these models have been applicable to all intravenously administered victim drugs. We derived and conducted a sensitivity/error analysis of a modification to the existing multiple mode interaction prediction model such that it is applicable to all intravenously administered victim drugs. Using this model we showed that ignoring the hepatic extraction ratio (EH) (as low as 0.3) of intravenously administered victim drugs can result in 1) substantial underestimation of f(m, CYPi) (the fraction of hepatic clearance of the victim drug via a given enzymatic pathway) and 2) error in dissecting the contribution of intestinal

SUBMITTER: Kirby BJ 

PROVIDER: S-EPMC2967394 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature