TY - JOUR

T1 - Pharmacokinetics and pharmacodynamics of vildagliptin in patients with type 2 diabetes mellitus.

AU - He, Yan-Ling

AU - Serra, Denise

AU - Wang, Yibin

AU - Campestrini, Joelle

AU - Riviere, Gilles-Jacques

AU - Deacon, Carolyn F

AU - Holst, Jens J

AU - Schwartz, Sherwyn

AU - Nielsen, Jace C

AU - Ligueros-Saylan, Monica

N1 - Keywords: Adamantane; Administration, Oral; Adult; Aged; Area Under Curve; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Half-Life; Humans; Hypoglycemic Agents; Male; Middle Aged; Nausea; Nitriles; Pyrrolidines; Treatment Outcome; Vomiting

PY - 2007

Y1 - 2007

N2 - BACKGROUND: Vildagliptin is a dipeptidyl peptidase IV (DPP-4) inhibitor currently under development for the treatment of type 2 diabetes mellitus. OBJECTIVES: To assess the pharmacokinetic and pharmacodynamic characteristics and tolerability of vildagliptin at doses of 10 mg, 25 mg and 100 mg twice daily following oral administration in patients with type 2 diabetes. METHODS: Thirteen patients with type 2 diabetes were enrolled in this randomised, double-blind, double-dummy, placebo-controlled, four-period, crossover study. Patients received vildagliptin 10 mg, 25 mg and 100 mg as well as placebo twice daily for 28 days. RESULTS: Vildagliptin was absorbed rapidly (median time to reach maximum concentration 1 hour) and had a mean terminal elimination half-life ranging from 1.32 to 2.43 hours. The peak concentration and total exposure increased in an approximately dose-proportional manner. Vildagliptin inhibited DPP-4 (>90%) at all doses and demonstrated a dose-dependent effect on the duration of inhibition. The areas under the plasma concentration-time curves of glucagon-like peptide-1 (GLP-1) [p < 0.001] and glucose-dependent insulinotropic peptide (GIP) [p < 0.001] were increased whereas postprandial glucagon was significantly reduced at the 25 mg (p = 0.006) and 100mg (p = 0.005) doses compared with placebo. As compared with placebo treatment, mean plasma glucose concentrations were decreased by 1.4 mmol/L with the vildagliptin 25 mg dosing regimen and by 2.5 mmol/L with the 100 mg dosing regimen, corresponding to a 10% and 19% reduction, respectively. Vildagliptin was generally well tolerated. CONCLUSION: Vildagliptin is likely to be a useful therapy for patients with type 2 diabetes based on the inhibition of DPP-4 and the subsequent increase in incretin hormones, GLP-1 and GIP, and the decrease in glucose and glucagon levels.

AB - BACKGROUND: Vildagliptin is a dipeptidyl peptidase IV (DPP-4) inhibitor currently under development for the treatment of type 2 diabetes mellitus. OBJECTIVES: To assess the pharmacokinetic and pharmacodynamic characteristics and tolerability of vildagliptin at doses of 10 mg, 25 mg and 100 mg twice daily following oral administration in patients with type 2 diabetes. METHODS: Thirteen patients with type 2 diabetes were enrolled in this randomised, double-blind, double-dummy, placebo-controlled, four-period, crossover study. Patients received vildagliptin 10 mg, 25 mg and 100 mg as well as placebo twice daily for 28 days. RESULTS: Vildagliptin was absorbed rapidly (median time to reach maximum concentration 1 hour) and had a mean terminal elimination half-life ranging from 1.32 to 2.43 hours. The peak concentration and total exposure increased in an approximately dose-proportional manner. Vildagliptin inhibited DPP-4 (>90%) at all doses and demonstrated a dose-dependent effect on the duration of inhibition. The areas under the plasma concentration-time curves of glucagon-like peptide-1 (GLP-1) [p < 0.001] and glucose-dependent insulinotropic peptide (GIP) [p < 0.001] were increased whereas postprandial glucagon was significantly reduced at the 25 mg (p = 0.006) and 100mg (p = 0.005) doses compared with placebo. As compared with placebo treatment, mean plasma glucose concentrations were decreased by 1.4 mmol/L with the vildagliptin 25 mg dosing regimen and by 2.5 mmol/L with the 100 mg dosing regimen, corresponding to a 10% and 19% reduction, respectively. Vildagliptin was generally well tolerated. CONCLUSION: Vildagliptin is likely to be a useful therapy for patients with type 2 diabetes based on the inhibition of DPP-4 and the subsequent increase in incretin hormones, GLP-1 and GIP, and the decrease in glucose and glucagon levels.

M3 - Journal article

C2 - 17596103

VL - 46

SP - 577

EP - 588

JO - Clinical Pharmacokinetics

JF - Clinical Pharmacokinetics

SN - 0312-5963

IS - 7

ER -