The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteers.
What is already known about this subject. Vildagliptin is a new, potent, and selective inhibitor of DPP-4. The efficacy and safety of vildagliptin in type 2 diabetes has been intensively studied in diverse subject populations. There has been little information published about the pharmacokinetics and pharmacodynamics of vildagliptin. What this study adds. No clinically relevant changes in pharmacokinetics or pharmacodynamics were observed between young and elderly, male and female, or high body mass index (BMI) and low BMI subjects. The results suggest that no dose modification is necessary for vildagliptin based on the age, gender, or BMI of a subject.


OBJECTIVE
To evaluate the effect of age, gender, and body mass index (BMI) on the pharmacokinetics and pharmacodynamics of vildagliptin.


METHODS
Forty healthy subjects received a single oral dose of 100 mg vildagliptin to assess the effects of age, gender, and BMI on the pharmacokinetics and pharmacodynamics, reflected by the time course of inhibition of DPP-4 activity, of vildagliptin.


RESULTS
Peak concentration and exposure (AUC((0-infinity))) of vildagliptin were 17% (90% CI 2, 35%) and 31% (90% CI 18, 45%) higher in elderly vs. young subjects. Renal clearance was reduced by 32% (90% CI 17, 45%) in elderly subjects. The pharmacokinetics of vildagliptin were not significantly influenced by gender or BMI. Inhibition of DPP-4 activity was similar regardless of age, gender, or BMI.


CONCLUSIONS
The pharmacokinetics of a single oral 100 mg dose of vildagliptin were not affected by gender and BMI. Exposure to vildagliptin was higher in elderly patients, but this was not associated with any difference in the effect of DPP-4 inhibition. Based on these results, no vildagliptin dose adjustment is necessary for age, gender, or BMI.
He
Yan-Ling
YL
Novartis Pharmaceuticals, Cambridge, MA, USA. yanling.he@novartis.com
Sabo
Ron
R
Campestrini
Joelle
J
Wang
Yibin
Y
Riviere
Gilles-Jacques
GJ
Nielsen
Jace C
JC
Rosenberg
Mitchell
M
Ligueros-Saylan
Monica
M
Howard
Dan
D
Dole
William P
WP
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D015992:Body Mass Index; D005260:Female; D006801:Humans; D008297:Male; D009570:Nitriles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D012727:Sex Characteristics; D000077597:Vildagliptin
D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; D000218:Adamantane