Figure 3.

(A) Effects of various intestinal transport inhibitors on the relative apparent permeability of ODSF across a Caco-2 cell monolayer. ***P<0.001 compared to the P_app of ODSF in the absence of all inhibitors (untreated control). (B) Prediction of a role for P-gp in intestinal absorption of ODSF. *P<0.05, **P<0.01, ***P<0.001 compared to the P_app (A to B) of ODSF in the absence of all inhibitors (untreated control); ^#P<0.05, ^###P<0.001 compared to the P_app (B to A) of ODSF in the absence of all inhibitors; ^$$$P<0.001 compared to the P_app (A to B) of ODSF in the absence of all inhibitors except Cys A. (C) P_app values with or without EGTA, in the presence or absence of all inhibitors except Cys A. **P<0.01, compared to the P_app without EGTA, in the absence of all inhibitors except Cys A; ^###P<0.001 compared to the P_app after treatment with EGTA, in the absence of all inhibitors except Cys A; ^$P<0.05 compared to the P_app without EGTA, in the presence of all inhibitors except Cys A.

Notes: Statistics: one-way ANOVA followed by the Tukey multiple comparisons test. Each value is mean±standard deviation (n=4 for each group).

Abbreviations: OP, oxaliplatin; DLM, N^α-deoxycholyl-l-lysyl-methylester; OP/DLM, ion-pairing complex between OP and DLM; P188, poloxamer 188; ODSF, solid oral formulation of OP/DLM with P188 and Labrasol; P-gp, P-glycoprotein; EGTA, ethylene glycol-bis-(2-aminoethyl ether)-N,N,N´,N´-tetraacetic acid; P_app, apparent permeability of ODSF across a Caco-2 cell monolayer; A to B, transport from apical to basal region; B to A, transport from basal to apical region; Act D, actinomycin D; CFZ, clofazimine; OST_α/β, organic solute transporter alpha/beta; MBCD, methyl-β-cyclodextrin; Cys A, cyclosporine A.