title: The effect of the once-daily human glucagon-like peptide 1 analog liraglutide on the pharmacokinetics of acetaminophen.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany. christoph.kapitza@profil.com
authors.forename: Christoph
authors.initials: C
authors.lastname: Kapitza
authors.forename: Milan
authors.initials: M
authors.lastname: Zdravkovic
authors.forename: Charlotte
authors.initials: C
authors.lastname: Hindsberger
authors.forename: Anne
authors.initials: A
authors.lastname: Flint
mesh_terms: D000082:Acetaminophen / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D018712:Analgesics, Non-Narcotic / Q000493:pharmacokinetics / Q000627:therapeutic use; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D004347:Drug Interactions; D005746:Gastric Emptying / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069450:Liraglutide; D008875:Middle Aged; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000082:Acetaminophen; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1