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As the research into the organic anion transporting polypeptides ( OATP s) continues to grow, it is important to ensure that the data generated are accurate and reproducible. In the  in vitro  evaluation of  OATP 1B1/1B3 inhibition, there are many variables that can contribute to variability in the resulting inhibition constants, which can then, in turn, contribute to variable results when clinical predictions ( R ‐values) are performed. Currently, the only experimental condition recommended by the  US  Food and Drug Administration ( FDA ) is the inclusion of a pre‐incubation period. 1  To identify other potential sources of variability, a descriptive analysis of available  in vitro  inhibition data was completed. For each of the 21 substrate/inhibitor pairs evaluated, cell type and pre‐incubation were found to have the greatest effect on half‐maximal inhibitory concentration ( IC  50 ) variability. Indeed, when only  HEK 293 cells and co‐incubation conditions were included, the observed variability for the entire data set (highest  IC  50 /lowest) was reduced from 12.4 to 5.2. The choice of probe substrate used in the study also had a significant effect on inhibitor constant variability. Interestingly, despite the broad range of inhibitory constants identified, these two factors showed little effect on the calculated  R ‐values relative to the  FDA  evaluation cutoff of 1.1 triggering a clinical evaluation for the inhibitors evaluated. However, because of the small data set available, further research is needed to confirm these preliminary results and define best practice for the study of  OATP s.

Variability in In Vitro OATP 1B1/1B3 Inhibition Data: Impact of Incubation Conditions on Variability and Subsequent Drug Interaction Predictions