Figure 2: Impact of the uptake transporter OATP1B1 on intracellular bioavailability (Fic).
From: Intracellular drug bioavailability: a new predictor of system dependent drug disposition
(a) Schematic representation of cell types used in this study: mock-transfected HEK293 cells express negligible levels of relevant drug-transporting proteins; OATP1B1-transfected HEK293 cells express OATP1B1. (b) Comparison between fu,cell in mock-transfected and OATP1B1-transfected HEK293 cells. Shaded area represents the impact of a theoretical error on fu,cell from measurements of fu,hom with 15% error. (c) Comparison between Fic in mock-transfected and OATP1B1-transfected HEK293 cells at 0.1 μM compound concentration. In b and c, negatively charged compounds at pH 7.4 are represented as triangles, neutral and zwitterionic species are represented by circles, and positively charged compounds are represented by squares. Substrates of OATP1B1 are highlighted in green. (d–g) Concentration-dependence of Fic in OATP1B1-transfected HEK293 cells (green filled squares), fitted with a sigmoidal model (green line), and mock-transfected HEK293 cells (blue circles) for atorvastatin (d), pitavastatin (e), fluvastatin (f), and simvastatin acid (g). For simvastatin acid, intracellular concentrations at 0.01 μM were below limit of quantification.
