title: Effect of exenatide on the steady-state pharmacokinetics of digoxin.
abstract: This open-label study investigated the effect of exenatide coadministration on the steady-state plasma pharmacokinetics of digoxin. A total of 21 healthy male subjects received digoxin (day 1, 0.5 mg twice daily; days 2-12, 0.25 mg once daily) and exenatide (days 8-12, 10 microg twice daily). Digoxin plasma and urine concentrations were measured on days 7 and 12. Exenatide coadministration did not change the overall 24-hour steady-state digoxin exposure (AUCtau,ss) and Cmin,ss but caused a 17% decrease in mean plasma digoxin Cmax,ss (1.40 to 1.16 ng/mL) and an increase in digoxin tmax,ss (median increase, 2.5 hours). Although the decrease in digoxin Cmax,ss was statistically significant, peak concentrations were within the therapeutic concentration range in all subjects. Digoxin urinary pharmacokinetic parameters were not altered. Gastrointestinal symptoms, the most common adverse effects of exenatide, decreased over time. Exenatide administration does not cause any changes in digoxin steady-state pharmacokinetics that would be expected to have clinical sequelae; thus, dosage adjustment does not appear warranted, based on pharmacokinetic considerations.
authors.affiliation: Global PK/PD and Trial Simulations, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Prajakti A
authors.initials: PA
authors.lastname: Kothare
authors.forename: Danny K W
authors.initials: DK
authors.lastname: Soon
authors.forename: Helle
authors.initials: H
authors.lastname: Linnebjerg
authors.forename: Soomin
authors.initials: S
authors.lastname: Park
authors.forename: Clark
authors.initials: C
authors.lastname: Chan
authors.forename: Adeline
authors.initials: A
authors.lastname: Yeo
authors.forename: Maggie
authors.initials: M
authors.lastname: Lim
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Mace
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wise
mesh_terms: D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004077:Digoxin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004347:Drug Interactions; D000077270:Exenatide; D006801:Humans; D008297:Male; D009325:Nausea / Q000139:chemically induced; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D010455:Peptides; D014688:Venoms; D004077:Digoxin; D000077270:Exenatide