Evaluation of pharmacokinetic interactions between vildagliptin and digoxin in healthy volunteers.
Vildagliptin is a novel antidiabetic agent that is an orally active, potent, and selective inhibitor of dipeptidyl peptidase IV, the enzyme responsible for degradation of the incretin hormones. This open-label, randomized, 3-period crossover study investigated the potential for pharmacokinetic interactions in 18 healthy subjects during coadministration of vildagliptin and digoxin. Subjects were randomized to receive each of 3 treatments: vildagliptin 100 mg qd, digoxin (0.5 mg, then 0.25 mg qd on days 2-7), and the combination vildagliptin/digoxin for 7 days. Coadministration of digoxin with vildagliptin had no effect on exposure to vildagliptin (geometric mean ratios [90% confidence interval]: AUC(0-24h), 0.99 [0.95-1.03]; C(max), 0.95 [0.85-1.06]) or to digoxin (AUC(0-24h), 1.02 [0.94-1.12]; C(max), 1.08 [0.97-1.20]). In addition, no changes in t(max), t((1/2)), and CL/F were observed for either drug. These results indicate that no dose adjustment is necessary when vildagliptin and digoxin are coadministered.
He
Yan-Ling
YL
Exploratory Development-DMPK, Novartis Institutes for Biomedical Research, 400 Technology Square, Building 605, Cambridge, MA 02139-3584, USA. yanling.he@novartis.com
Sabo
Ron
R
Sunkara
Gangadhar
G
Bizot
Marie-Noëlle
MN
Riviere
Gilles-Jacques
GJ
Leon
Selene
S
Ligueros-Saylan
Monica
M
Dole
William P
WP
Howard
Dan
D
D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004077:Digoxin / Q000009:adverse effects / Q000493:pharmacokinetics*; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000493:pharmacokinetics*; D011759:Pyrrolidines / Q000009:adverse effects / Q000493:pharmacokinetics*; D000077597:Vildagliptin
D000889:Anti-Arrhythmia Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D009570:Nitriles; D011759:Pyrrolidines; D004077:Digoxin; D000077597:Vildagliptin; D000218:Adamantane