Endogenous biomarkers of drug transporters are promising tools to evaluate in vivo transporter function and potential alterations in the pharmacokinetics of their substrates. We have previously reported that coproporphyrin I/III captured the weak inhibition of OATP1B transporters by GDC-0810. In this study, we measured plasma concentrations of additional biomarkers, namely fatty acids, bile acids and their sulphate or glucuronide conjugates in the presence and absence of GDC-0810. Concentrations of hexadecanedioate and tetradecanedioate did not increase in the presence of GDC-0810. Among bile acids and their conjugates, glycochenodeoxycholate and glycodeoxycholate 3-O-glucuronides (GCDCA-3G and GDCA-3G) showed Cmax increases with geometric mean ratio (95% confidence interval) of 1.58 (1.13-2.22) and 1.49 (1.21-1.83), consistent with previous reports from low-dose rifampin co-administration and pharmacogenetic studies. These results suggest that GCDCA-3G and GDCA-3G are two more promising biomarkers that may capture weak OATP1B inhibition in addition to coproporphyrin I/III.
Keywords: OATP1B; biomarkers; drug transporters; drug-drug interaction.
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