Supplemental Table 1. Summary of preclinical and clinical evaluation of the endogenous biomarkers for hepatic transporters Biomarkers Transporter In vivo studies in cynomolgus monkeys In vivo studies in humans References substratesa Fold change of Fold Inhibitor Fold change Fold Inhibitor plasma AUC change of of plasma change of urinary AUC or urinary excretion Cmax excretion OATP1B - Rifampin 2.1-(total); - Rifampin 1, 2 bilirubin (18mg/kg, (600mg, SD, PO) SD, PO) OATP1B 1.2- - Rifampin - - - 3 sulfate (DHEAS) (2mg/kg, SD, PO) 2.0- - Rifampin (10mg/kg, SD, PO) Coproporphyrin I (CPI) OATP1B 2.6-(CPI); 3.4-(CPI); Cyclosporin 4.0-(CPI); 3.6-(CPI); Rifampin 4,5 and III (CPIII) 1.6-(CPIII) A 3.3-(CPIII) 1.7-(CPIII) (600mg (100mg/kg, SD, PO) SD, PO) 2.6-(CPI); 4.1-(CPI); Rifampin 2.8-(CPIII) (15mg/kg, SD, PO) Tetradecanedioate OATP1B1, - - - 1.4-(TDA); - 6 (TDA) and OAT1, OAT3 1.5-(HDA) A hexadecanedioate (100mg (HDA) BID, PO)
Supplemental Table 1. Summary of preclinical and clinical evaluation of the endogenous biomarkers for hepatic transporters Biomarkers Transporter substratesa In vivo studies in cynomolgus monkeys In vivo studies in humans References Fold change of plasma AUC Fold change of urinary excretion Inhibitor Fold change of plasma AUC or Cmax Fold change of urinary excretion Inhibitor bilirubin OATP1B - Rifampin (18mg/kg, SD, PO) 2.1-(total); - Rifampin (600mg, SD, PO) 1, 2 sulfate (DHEAS) OATP1B 1.2- - Rifampin (2mg/kg, SD, PO) - - - 3 2.0- - Rifampin (10mg/kg, SD, PO) Coproporphyrin I (CPI) and III (CPIII) OATP1B 2.6-(CPI); 3.4-(CPI); 1.6-(CPIII) Cyclosporin A (100mg/kg, SD, PO) 4.0-(CPI); 3.3-(CPIII) 3.6-(CPI); 1.7-(CPIII) Rifampin (600mg SD, PO) 4,5 2.6-(CPI); 4.1-(CPI); 2.8-(CPIII) Rifampin (15mg/kg, SD, PO) Tetradecanedioate (TDA) and hexadecanedioate (HDA) OATP1B1, OAT1, OAT3 - - - 1.4-(TDA); 1.5-(HDA) - A (100mg BID, PO) 6