title: Pharmacokinetic and pharmacodynamic interaction of vildagliptin and voglibose in Japanese patients with Type 2 diabetes.
abstract: OBJECTIVE
  To assess the extent of pharmacokinetic and pharmacodynamic interaction between vildagliptin, a potent and selective inhibitor of dipeptidyl peptidase IV (DPP-4) enzyme, and voglibose, an α-glucosidase inhibitor widely prescribed in Japan, when coadministered in Japanese patients with Type 2 diabetes.
  
  
  METHODS
  In this open-label, randomized, 3-treatment, 3-period and 6-way crossover study, 24 Japanese patients with Type 2 diabetes received 50 mg vildagliptin twice daily; 50 mg vildagliptin twice daily co-administered with 0.2 mg voglibose three times daily; or 0.2 mg voglibose three times daily for 3 days in each period. Plasma concentrations of vildagliptin, DPP-4, glucagon-like peptide-1 (GLP-1), glucose, insulin, and glucagon were determined from blood samples collected at steady state.
  
  
  RESULTS
  Exposure to vildagliptin 50 mg (area under the concentration-time curve from 0 to 12 hours (AUCτ,ss)) and maximum plasma concentration at steady state (Cmax,ss) was reduced by 23% and 34% respectively with co-administration of voglibose. The percentage of DPP-4 inhibition by vildagliptin remained unchanged when vildagliptin was given alone or co-administered with voglibose; maximum inhibition was 98.3 ± 1.4% (mean ± SD) for vildagliptin alone and 97.4 ± 1.1% with co-administration. Coadministration of vildagliptin and voglibose led to a greater increase in the active GLP-1 plasma concentration than did vildagliptin alone (geometric mean ratio 1.63 (90% CI, 1.30, 2.03), p = 0.0007). The combination of vildagliptin and voglibose also led to a significantly lower plasma glucose levels (p < 0.0001).
  
  
  CONCLUSIONS
  Plasma vildagliptin levels were decreased when voglibose was co-administered, although DPP- 4 inhibition remained unchanged. Co-administration led to significantly better pharmacodynamic response compared with each treatment alone, including higher active GLP-1 and lower glucose levels. The results indicate that this coadministration may be beneficial in the clinical situation. Vildagliptin and voglibose treatments, alone or when co-administered, were well tolerated in Japanese patients with Type 2 diabetes.
authors.affiliation: Novartis Pharma K.K, Tokyo, Japan. masayuki.yamaguchi@novartis.com
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Takami
authors.initials: T
authors.lastname: Saji
authors.forename: Sachiko
authors.initials: S
authors.lastname: Mita
authors.forename: Kenneth
authors.initials: K
authors.lastname: Kulmatycki
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: He
authors.forename: Kenichi
authors.initials: K
authors.lastname: Furihata
authors.forename: Kaneo
authors.initials: K
authors.lastname: Sekiguchi
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000493:pharmacokinetics* / Q000494:pharmacology; D011759:Pyrrolidines / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077597:Vildagliptin
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D007294:Inositol; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077597:Vildagliptin; D000218:Adamantane; C102817:voglibose