Pharmacokinetic Analysis of OATP1B Modulation

Pharmacokinetic parameters were derived from non-compartmental analysis using Phoenix WinNonlin version 8.0 (Certara, Princeton, NJ, USA). The peak plasma concentration (C_max) was determined by visual inspection of the data from the concentration–time curves. The linear trapezoidal rule was used to obtain the area under the plasma concentration–time curve (AUC). The C_max to baseline ratio (C_maxR) instead of the reference method that relies on the AUC to control ratio (AUCR) was used to evaluate the modulation of OATP1B function, as samples from an untreated group were not available in our study, and previous studies [13 (link),20 (link)] reported that such an approach provides data of equivalent utility. In the calculation of C_max ratio of the endogenous biomarkers, the control values were set as the baseline concentration of corresponding patient.