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.

Effects of Multiple Doses of Albiglutide on the Pharmacokinetics, Pharmacodynamics, and Safety of Digoxin, Warfarin, or a Low-Dose Oral Contraceptive

“…These findings are consistent with results of previous studies, suggesting no significant PK effect of other GLP-1 analogs on digoxin, warfarin, or EE. [30][31][32] Minor increases in C max for digoxin and NE were seen that were slightly higher than the upper limit of the 90% CI, but these were not considered clinically relevant. In both cases, the magnitude and direction of the effects were not expected to impact the efficacy or safety of these agents.…”

Clinical Pharmacology of Albiglutide, a GLP-1 Receptor Agonist

“…The results indicate that no dose adjustments of digoxin are required when coadministered with albiglutide, consistent with findings reported with other approved GLP-1R agonists. 65,66 Coadministration With Anticoagulant Warfarin Warfarin has a narrow therapeutic index and has been the subject of many DDI studies because minimal effects on the PK of warfarin can have a large impact on its PD, resulting in failure of therapy or safety/tolerability issues. The impact of steady-state albiglutide on single-dose warfarin PK was evaluated in an open-label, sequential, single-center study (N = 16) in healthy male and female volunteers.…”

Validation and application of a 96-well format solid-phase extraction and liquid chromatography–tandem mass spectrometry method for the quantitation of digoxin in human plasma

“…Almost all digoxin interaction studies have been carried out at the maintenance dose of 0.25 mg. The mean C max in these studies ranged from 1.16 to 3.70 ng/mL (Table 1) [4][5][6][7][8][9][10]. Depending on the situation, side effects may be caused by exceeding the upper limit of recommended therapeutic plasma concentration.…”