Aprepitant is a highly selective
neurokinin-1 receptor antagonist that, in combination with a
corticosteroid and a 5-hydroxytryptamine3 (5HT3) receptor antagonist, has been shown to be efficacious in the prevention of highly emetogenic
chemotherapy-induced
nausea and
vomiting. In vitro data suggest that
aprepitant is a substrate and a weak inhibitor of
P-glycoprotein. Thus, the effect of
aprepitant on the pharmacokinetics of
digoxin, a
P-glycoprotein substrate, was examined in a double-blind, placebo-controlled, randomized, two-period crossover study in 12 healthy subjects. Each subject received daily oral doses of
digoxin 0.25 mg on Days 1 through 13 during both treatment periods.
Aprepitant 125 mg (or matching placebo) was coadministered orally with
digoxin on Day 7, and
aprepitant 80 mg (or matching placebo) was coadministered orally with
digoxin on Days 8 to 11.
Aprepitant did not affect the pharmacokinetics of
digoxin. The geometric mean ratios (90% confidence interval [CI]) for plasma AUC0-24 h of
digoxin (with/without
aprepitant) were 0.99 (0.91, 1.09) and 0.93 (0.83, 1.05) on Days 7 and 11, respectively, and the geometric mean ratios (90% CI) for the 24-hour urinary excretion of immunoreactive
digoxin (with/without
aprepitant) were 0.91 (0.80, 1.04) and 1.00 (0.91, 1.09) on Days 7 and 11, respectively. Thus,
aprepitant, when dosed as a 5-day regimen, did not interact with a known substrate of the
P-glycoprotein transporter.