Assessment of pharmacokinetic drug-drug interaction between pradigastat and acetaminophen in healthy subjects

The purpose of this study was to evaluate the effect of pradigastat, a diacylglycerol acyltransferase-1 inhibitor, on the pharmacokinetics of acetaminophen, a gastric emptying marker. Twenty-five healthy subjects were enrolled and received 1000 mg acetaminophen with meal in period 1, pradigastat (100 mg x 3 days followed by 40 mg x 7 days, 1 h before meal) in period 2, and 1000 mg acetaminophen at -2, -1, 0, +1, and +3 h with respect to meal timing in presence of steady-state pradigastat (40-mg maintenance dose) during periods 3-7. The geometric mean ratio and 90 % confidence interval of Cmax and AUC of acetaminophen were within 80-125 % suggesting that the rate ad extent of acetaminophen were not affected when given at various time points with respect to pradigastat/meal timing. The acetaminophen Tmax was also not impacted under all treatment conditions but increased from 0.75 to 2.00 h when administered 1 h after food. In the presence of steady-state pradigastat, the pharmacokinetics of acetaminophen is unchanged, when given before, with, or 3 h after a meal. However, when given 1 h after a meal, the T-max of acetaminophen was delayed by similar to 1.25 h without affecting C-max or AUC.