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Dose Proportionality and the Effect of Food on Vildagliptin, a Novel Dipeptidyl Peptidase IV Inhibitor, in Healthy Volunteers
Author(s) -
Sunkara Gangadhar,
Sabo Ron,
Wang Yibin,
He YanLing,
Campestrini Joelle,
Rosenberg Mitchell,
Howard Dan,
Dole William P.
Publication year - 2007
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270007304313
Subject(s) - vildagliptin , pharmacokinetics , crossover study , dipeptidyl peptidase 4 , pharmacology , linagliptin , medicine , glycemic , half life , dipeptidyl peptidase 4 inhibitor , dipeptidyl peptidase , type 2 diabetes , diabetes mellitus , chemistry , endocrinology , enzyme , biochemistry , placebo , alternative medicine , pathology
Vildagliptin is a potent and selective dipeptidyl peptidase IV inhibitor in development for the treatment of type 2 diabetes that improves glycemic control by enhancing α‐ and β‐cell responsiveness to glucose. Two open‐label, single‐dose, randomized, crossover studies in healthy subjects (ages 18–45 years) investigated the dose proportionality of vildagliptin pharmacokinetics (n = 20) and the effect of food (n = 24) on vildagliptin pharmacokinetics. There was a linear relationship ( r 2 = 0.999) between vildagliptin doses of 25, 50, 100, and 200 mg and area under the plasma concentration‐time curve from time zero to infinity (AUC 0–∞ ) and maximum plasma concentration (C max ). Dose proportionality was assessed using a statistical power model [X = α·(dose) β ]. The 90% confidence intervals of the proportionality coefficient, β, for AUC 0–∞ (1.15–1.19) and C max (1.04–1.14) indicated that deviations from dose proportionality were small (<7.7%). Doubling of dose led to 2.1‐ to 2.3‐fold increases in AUC 0–∞ and C max but no dose‐dependent changes in time to reach C max or terminal elimination half‐life. Administration of vildagliptin 100 mg following a high‐fat meal decreased C max by 19% and AUC 0–∞ by 10%. Vildagliptin displays approximately dose‐proportional pharmacokinetics over the 25‐ to 200‐mg dose range, and administration with food has no clinically relevant effect on vildagliptin pharmacokinetics.