Fig. 4.
Effect of intestinal metabolism on apparent permeability of AZD1283 in human jejunal tissue (n = 2) in Ussing chamber. Differences in permeability between AZD1283 and 14C radio-labelled AZD1283 is shown. a P app in the mucosa to serosa direction at 10, 30, 70 and 100 uM for unchanged AZD1283 (black bars) and for total 14C radio-labelled AZD1283, e.g. contributions from unchanged parent and its metabolites (red bars). b P app in the serosa to mucosa direction at identical concentrations of unchanged AZD1283 (black bars) and total 14C radio-labelled AZD1283 (red bars). c Apparent extraction ratio (App E g) calculated from the equation App E g = (P total − P unchanged) / (P total). The methodology and approach have been described elsewhere (36). d–f Analogous permeability plots to a–c tested at 30 and 70 uM and from the colon (n = 1) rather than the jejunal tissue