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

Eur J Clin Pharmacol. 2015 Apr;71(4):425-32. doi: 10.1007/s00228-015-1822-2. Epub 2015 Mar 1.

Abstract

Purpose: 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.

Methods: Twenty-five healthy subjects were enrolled and received 1000 mg acetaminophen with meal in period 1, pradigastat (100 mg × 3 days followed by 40 mg × 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.

Results: 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.

Conclusion: 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 Tmax of acetaminophen was delayed by ∼1.25 h without affecting Cmax or AUC.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / pharmacokinetics*
  • Acetates / pharmacology*
  • Adult
  • Aminopyridines / pharmacology*
  • Area Under Curve
  • Cross-Over Studies
  • Diacylglycerol O-Acyltransferase / antagonists & inhibitors
  • Drug Interactions / physiology*
  • Female
  • Gastric Emptying / physiology
  • Healthy Volunteers
  • Humans
  • Male
  • Middle Aged
  • Young Adult

Substances

  • Acetates
  • Aminopyridines
  • pradigastat
  • Acetaminophen
  • Diacylglycerol O-Acyltransferase