Maralixibat

Following single oral administration of maralixibat in healthy adults at doses ranging from 1 mg to 500 mg, plasma concentrations of maralixibat were below the limit of quantification (0.25 ng/mL) at doses less than 20 mg and PK parameters could not be reliably estimated.^L48081 Following a single dose administration of 30 mg under fasted conditions, median T_max was 0.75 and mean (SD) C_max and AUC_last were 1.65 (1.10) ng/ml and 3.43 (2.13) ng·h/mL, respectively.^L48081 Maralixibat is minimally absorbed and plasma concentrations are often below the limit of quantification (0.25 ng/mL) after single or multiple doses at recommended doses. Following a single oral administration of maralixibat 30, 45, and 100 mg liquid formulation under fasted conditions, AUC_last and C_max increased in a dose-dependent manner with increases of 4.6-and 2.4-fold, respectively, following a 3.3-fold dose increase from 30 to 100 mg.^L48081 No accumulation of maralixibat was observed following repeated oral administration of maralixibat in healthy adults at doses up to 100 mg once daily.^L48081 Concomitant administration of a high-fat meal with a single oral dose of maralixibat decreased both the rate and extent of absorption. AUC and C_max of maralixibat values in the fed state were 64.8% to 85.8% lower relative to oral administration of 30 mg in fasted conditions. The effect of food on the changes of systemic exposures to maralixibat is not clinically significant.^L48081