title: Effect of exenatide on the pharmacokinetics and pharmacodynamics of warfarin in healthy Asian men.
abstract: Exenatide, a treatment for type 2 diabetes, slows gastric emptying as part of its pharmacologic action and may alter the absorption of concomitant oral drugs. This open-label, 2-period, fixed-sequence study evaluated the influence of exenatide coadministration on the pharmacokinetics and pharmacodynamics of warfarin, a narrow therapeutic index drug, in healthy men (N = 16). A single, 25-mg oral dose of warfarin, with a standardized breakfast, was administered alone in period 1 and concomitantly with 10 microg exenatide subcutaneous twice daily in period 2. Exenatide did not produce significant changes in R- or S-warfarin pharmacokinetics. Although there were minor reductions in warfarin anticoagulant effect, the ratios of geometric means for the area under the international normalized ratio (INR)-time curve from dosing until the time of the last measurable INR value or maximum-observed INR response being 0.94 (0.93-0.96) and 0.88 (0.84-0.92), respectively, the magnitude and direction of these changes do not suggest a safety concern from this interaction.
authors.affiliation: Lilly-NUS Centre for Clinical Pharmacology, Level 6, Clinical Research Centre, MD 11, National University of Singapore, 10 Medical Drive, Singapore 117597, Singapore. soon_danny@lilly.com
authors.forename: Danny
authors.initials: D
authors.lastname: Soon
authors.forename: Prajakti A
authors.initials: PA
authors.lastname: Kothare
authors.forename: Helle
authors.initials: H
authors.lastname: Linnebjerg
authors.forename: Soomin
authors.initials: S
authors.lastname: Park
authors.forename: Eunice
authors.initials: E
authors.lastname: Yuen
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Mace
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wise
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D044466:Asian People; D002853:Chromatography, Liquid / Q000379:methods; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000077270:Exenatide; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D007279:Injections, Subcutaneous; D019934:International Normalized Ratio / Q000379:methods; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014859:Warfarin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D000925:Anticoagulants; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D014859:Warfarin; D000077270:Exenatide; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases