Vildagliptin, a novel dipeptidyl peptidase IV inhibitor, has no pharmacokinetic interactions with the antihypertensive agents amlodipine, valsartan, and ramipril in healthy subjects.
We conducted 3 open-label, multiple-dose, 3-period, randomized, crossover studies in healthy subjects to assess the potential pharmacokinetic interaction between vildagliptin, a novel dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes, and representatives of 3 commonly prescribed antihypertensive drug classes: (1) the calcium channel blocker, amlodipine; (2) the angiotensin receptor blocker, valsartan; and (3) the angiotensin-converting enzyme inhibitor, ramipril. Coadministration of vildagliptin 100 mg with amlodipine 5 mg, valsartan 320 mg, or ramipril 5 mg had no clinically significant effect on the pharmacokinetics of these drugs. The 90% confidence intervals of the geometric mean ratios for area under the plasma concentration-time curve from time zero to 24 hours (AUC0-24h) and maximum plasma concentration (Cmax) for vildagliptin, amlodipine, and ramipril (and its active metabolite, ramiprilat) were contained within the acceptance range for bioequivalence (0.80-1.25). Valsartan AUC0-24h and Cmax increased by 24% and 14%, respectively, following coadministration of vildagliptin, but this was not considered clinically significant. Vildagliptin was generally well tolerated when given alone or in combination with amlodipine, valsartan, or ramipril in healthy subjects at steady state. No adjustment in dosage based on pharmacokinetic considerations is required should vildagliptin be coadministered with amlodipine, valsartan, or ramipril in patients with type 2 diabetes and hypertension.
He
Yan-Ling
YL
Exploratory Development-DMPK, Novartis Institutes for Biomedical Research, 400 Technology Square, Building 605, Cambridge, MA 02139-3584, USA.
Ligueros-Saylan
Monica
M
Sunkara
Gangadhar
G
Sabo
Ron
R
Zhao
Charlie
C
Wang
Yibin
Y
Campestrini
Joelle
J
Pommier
Francoise
F
Dole
Kiran
K
Marion
Alan
A
Dole
William P
WP
Howard
Dan
D
D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000328:Adult; D017311:Amlodipine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D018592:Cross-Over Studies; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006261:Headache / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D017257:Ramipril / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D013607:Tablets; D013777:Tetrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D014633:Valine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000068756:Valsartan; D000077597:Vildagliptin
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D013607:Tablets; D013777:Tetrazoles; D017311:Amlodipine; C052549:ramiprilat; D000068756:Valsartan; D014633:Valine; D000077597:Vildagliptin; D017257:Ramipril; D000218:Adamantane