The effect of the once-daily human glucagon-like peptide 1 analog liraglutide on the pharmacokinetics of acetaminophen

Introduction Acetaminophen is a commonly used analgesic and antipyretic drug, and is frequently used to study gastric emptying. Due to its high permeability and high solubility, acetaminophen can be used as a pharmacologic model for medications with similar characteristics. The objective of this study was to assess the effect of liraglutide on the pharmacokinetics (PK) of acetaminophen in patients with type 2 diabetes. Methods This was a randomized, placebo-controlled, two-period crossover trial in which subjects with type 2 diabetes received placebo or liraglutide. After steady state PK of liraglutide 1.8 mg/ placebo were established, a single dose of acetaminophen 1 g was administered at the time of liraglutide C max (maximum concentration). The PK profile of acetaminophen was assessed at 18 time points during the 8-hour post-dosing period. Placebo and liraglutide were considered equivalent with respect to area under the curve (AUC) 0−∞ and AUC 0−480 min of acetaminophen if the 90% CI for the ratio was fully contained within the limits of 0.80 to 1.25. Results All subjects ( n =18; mean [SD] age 59 [7] years, body mass index [BMI] 29.7 [4.2] kg/m 2 , and glycated hemoglobin [HbA 1c ] 7.8% [0.6%]) completed the study. Equivalence was demonstrated between liraglutide 1.8 mg at steady state and placebo, with respect to acetaminophen AUC 0−∞ (estimated ratio 1.04; 90% CI: 0.97, 1.10) and acetaminophen AUC 0-480 min (estimated ratio 0.95; 90% CI: 0.89, 1.01). During liraglutide, a lower C max was observed (estimated ratio 0.69; 90% CI: 0.56, 0.85) and the median acetaminophen t max occurred 15 minutes later compared with placebo. Conclusion The overall exposure of acetaminophen following a 1 g dose was comparable for subjects taking liraglutide or placebo, and the clinical impact of the lower C max and delay in absorption of acetaminophen was considered to be transient and small, and without clinical relevance. No adjustment for acetaminophen is recommended when used concomitantly with liraglutide.