title: Effects of meal timing relative to dosing on the pharmacokinetics and pharmacodynamics of vildagliptin in Japanese patients with Type 2 diabetes.
abstract: OBJECTIVE
  To assess the effects of meal timing on the pharmacokinetics and pharmacodynamics of the dipeptidyl peptidase IV (DPP-4) inhibitor vildagliptin in Japanese patients with Type 2 diabetes.
  
  
  METHODS
  In this open-label, single-center crossover study, 12 Japanese patients with Type 2 diabetes were randomized to twice-daily vildagliptin 50 mg, administered 30 min before or immediately before breakfast and dinner for 7 days. After a 7-day washout period, patients received the other regimen. Blood samples were collected for the determination of vildagliptin, DPP-4, glucagon-like peptide-1 (GLP-1) and glucose.
  
  
  RESULTS
  Vildagliptin absorption appeared slower when administered 30 min before rather than immediately before meals (tmax absolute range: 1.00 - 2.00 h vs. 0.33 - 1.58 h). Vildagliptin Cmax and AUC0-8 h were essentially the same irrespective of meal timing (geometric mean ratio: Cmax 1.08 (90% CI; 0.92 - 1.26); AUC0-8 h 0.97 (90% CI; 0.91 - 1.05)). Meal timing did not affect pharmacodynamics; complete DPP-4 inhibition (> 90%) was sustained for 8 h post-dose, and plasma active glucagon-like peptide-1 levels increased 2 - 3-fold from baseline. Fasting plasma glucose (FPG) and postprandial plasma glucose (PPPG) reductions from baseline did not differ significantly with meal timing (30 min before vs. immediately before: FPG, -8.9 vs. -5.8 mg/dl; adjusted AUE0-4 h, -67.0 vs. -51.0 mg×h/dl). Vildagliptin was well tolerated.
  
  
  CONCLUSIONS
  Dosing 30 min or immediately before meals did not affect vildagliptin pharmacokinetics or pharmacodynamics in Japanese patients with Type 2 diabetes.
authors.affiliation: Novartis Institutes for BioMedical Research Inc., Cambridge, MA 02139-3584, USA. yanling.he@novartis.com
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: He
authors.forename: Harunobu
authors.initials: H
authors.lastname: Ito
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Terao
authors.forename: Sayaka
authors.initials: S
authors.lastname: Shimada
authors.forename: Shin
authors.initials: S
authors.lastname: Irie
authors.forename: Kaneo
authors.initials: K
authors.lastname: Sekiguchi
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D044466:Asian People; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D004435:Eating; D005247:Feeding Behavior; D005260:Female; D018565:Food-Drug Interactions; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007408:Intestinal Absorption; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D019518:Postprandial Period; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome; D000077597:Vildagliptin
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; D000077597:Vildagliptin; D000218:Adamantane