Fig. 2.
Impact of FG on estimating intestinal contribution to DDIs. The effect of ignoring the EH of 0.25 across varying FG values for an intravenously administered victim drug when the effect of a DDI on intestinal enzymes is estimated shows the following. A, the percent error in the estimated fraction of intestinal intrinsic clearance remaining (fClintGI) increases to greater than 200% as fold induction increases above 2- to 3-fold irrespective of FG and is greatly underpredicted by as much as −100% for 90% inhibition (fClintHep and fClintGI = 0.1) for FG >0.3. B, the percent error in the predicted FG′/FG ratio is independent of FG. Note: the fraction of hepatic (fClintHep) and intestinal (fClintGI) intrinsic clearance remaining was set equal and varied between 25 and 0.0001; intestinal bioavailability was varied between 0.1 and 0.9. The fraction of hepatic (fClintHep) and intestinal (fClintGI) clearance remaining axes are on a logarithmic scale.