A comparative pharmacodynamic and pharmacokinetic study of Vildagliptin SR 100 mg tablet in normal healthy adult male subjects

Abstract

Background: Vildagliptin, a potent dipeptidyl peptidase IV inhibitor (DPP-4i), is usually administered twice daily to provide ≥90% inhibition of DPP-4 over 24 hours. Considering most type 2 diabetes (T2D) patients are on multiple medications, reducing dosing and pill burden can increase patient convenience. A 100 mg Vildagliptin sustained release (SR) formulation that would inhibit DPP-4 ≥ 80% over 24 hours with a lower dosing frequency was developed. The study was thus conducted to evaluate the pharmacodynamics, pharmacokinetics, and safety profile of once-daily Vildagliptin SR compared to twice-daily Vildagliptin immediate-release (IR) formulation.
 Results: Twenty-four healthy adult male subjects were enrolled, and 22 completed the clinical phase of the study. The DPP-4 inhibition over time was comparable between the formulations. At 24 hrs single dose of once-daily Vildagliptin SR 100 mg tablet inhibited DPP4 by 89.58%, whereas twice-daily Vildagliptin IR 50 mg by 91.052%. The pharmacokinetic parameters like peak plasma concentration (Cmax), area under the plasma concentration-time curve from 0 hours to the last measurable concentration (AUC0-t) and AUC-time curve up to infinity (AUC0-inf) were not significantly different in both groups. Besides this, both groups reported no serious adverse effects during the study period.
 Conclusion: The above result shows that once-daily Vildagliptin SR 100 mg is bioequivalent to twice-daily Vildagliptin IR 50 mg. Moreover, the ability of Vildagliptin SR 100 mg to provide above 80% DPP-4 inhibition coverage over 24 hrs may help to achieve a clinically meaningful glucose-lowering effect and reduce the pill burden in diabetes patients.
 Keywords: Vildagliptin, dipeptidyl peptidase IV inhibitor (DPP-4i), type 2 diabetes (T2D) patients, pharmacokinetic parameters

Pharmacokinetic and Pharmacodynamics Study of Multiple Oral Doses of Vildagliptin Sustained Release 100 Mg Tablets under the Fed State in Healthy Volunteers

“…Similar to this, a study by Joshi et al under fasting conditions showed that vildagliptin SR 100 mg is bioequivalent to vildagliptin 50 mg and provides 80% DPP4 inhibition for 24 hours, thus improving glycemic control while decreasing the frequency of medication intake. 12 Evidence suggests that vildagliptin SR 100 mg once daily is equally efficacious and safe as vildagliptin 50 mg twice daily. The result of a randomized, open-label, phase 4 and clinical trial conducted on Indian patients showed that vildagliptin 100 mg SR once daily is equally effective as 50 mg twice daily vildagliptin in reducing HbA1C, fasting, and postprandial blood glucose levels when used along with metformin.…”