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


CONCLUSIONS
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.
Novartis Institutes for BioMedical Research, East Hanover, NJ, USA.
Surya
S
Ayalasomayajula
Dan
D
Meyers
Phillip
P
Koo
Atish
A
Salunke
Tapan
T
Majumdar
Sam
S
Rebello
Gangadhar
G
Sunkara
Jin
J
Chen
D000082:Acetaminophen / Q000493:pharmacokinetics*; D000085:Acetates / Q000494:pharmacology*; D000328:Adult; D000631:Aminopyridines / Q000494:pharmacology*; D019540:Area Under Curve; D018592:Cross-Over Studies; D051048:Diacylglycerol O-Acyltransferase / Q000037:antagonists & inhibitors; D004347:Drug Interactions / Q000502:physiology*; D005260:Female; D005746:Gastric Emptying / Q000502:physiology; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
D000085:Acetates; D000631:Aminopyridines; C000594809:pradigastat; D000082:Acetaminophen; D051048:Diacylglycerol O-Acyltransferase