Premium
PII‐12
Author(s) -
He Y. L.,
Sabo R.,
Balez S.,
Wang Y.,
Campestrini J.,
Marion A.,
LiguerosSaylan M.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.137
Subject(s) - vildagliptin , bioavailability , confidence interval , medicine , urine , oral administration , volume of distribution , pharmacokinetics , excretion , distribution (mathematics) , pharmacology , bioequivalence , type 2 diabetes , diabetes mellitus , endocrinology , mathematical analysis , mathematics
OBJECTIVES Vildagliptin (V) is a potent and specific DPP‐4 inhibitor, which is developed for treatment of type 2 diabetes (T2D). The objective of this study was to investigate the absolute bioavailability (F) of V after oral and intravenous (iv) administration of V. METHODS This was an open label, single‐dose, randomized, cross‐over study in healthy volunteers. Thirteen subjects were enrolled and 12 completed the study. Each subject was randomly assigned to receive one of the two treatments in a sequential manner with 72‐hr interval between treatment periods: 50 mg po or 25 mg iv infusion over 30 minutes. Blood samples were collected after oral and iv administrations and the concentrations were measured by LC‐MS/MS. RESULTS The absolute oral F of V was estimated to be 85% with a 90% confidence interval over the range between 79 and 91%. After iv infusion, the total body clearance (CL tot ) and the renal clearance (CL R ) were 40.6±8.97 L/hr and 13.0±2.35 L/hr, respectively, demonstrating that CL R accounted for 33% of the CL tot . The volume of distribution at steady‐state was 70.5±16.1 L, suggesting that V distributes into tissues and organs. CONCLUSIONS The oral absolute F of V was 85%. The total recovery of radioactivity in urine when[ 14 C]‐V was given orally in a previous study was also ∼85%, suggesting that hepatic excretion has little contribution to the elimination of V. Single oral and iv administrations of V were well tolerated in this small number of healthy subjects. Clinical Pharmacology & Therapeutics (2005) 79 , P38–P38; doi: 10.1016/j.clpt.2005.12.137