Clinical pharmacokinetics and pharmacodynamics of vildagliptin 50 mg sustained release tablet formulation in healthy Indian males after single and multiple-dose

Abstract

Background: Vildagliptin 50 mg once-daily is a clinically established anti-diabetic therapy in combination with a sulphonylurea and renally impaired patients. We developed sustained release (SR) vildagliptin 50 mg tablet formulation for prolongation of dipeptidyl peptidase-4 (DPP-4) inhibition coverage. The present study compares the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of investigational vildagliptin SR 50 mg tablet with Galvus® in healthy Indian adult males after single and multiple-dose administration.Methods: Each randomized, open-label, two-period, cross-over study enrolled 36 healthy Indian adult male subjects for the assessment of single and multiple-dose PK/PD profiles of SR 50 mg vildagliptin under fed condition. The plasma drug concentrations were quantified using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. PK parameters (Cmax (ng/ml), AUC0-18, AUC0-36, and AUC0-τ (ng.hr/ml), Tmax (hour), t1/2 (hour), Tmaxss (hour), Cτss (ng.hr/ml) were calculated using Phoenix® WinNonlin® software. The DPP-4 inhibition was determined in a fluorescence-based assay.Results: Vildagliptin SR tablet showed prolonged PK/PD characters compared to Galvus®. All PK parameters expressed as Mean±SD. The single-dose PK measures were Cmax (58.22±11.31), AUC0-18 (556.92±135.84), AUC0-36 (608.82±159.84), Tmax (6.48±3.78). In the multiple-dose study, PK findings were Cmax (73.20±17.71), AUC0-τ (714.36±303.21), Cτss (4.15±6.51), Tmaxss (5.60±3.12). Vildagliptin SR 50 mg achieved prolonged DPP-4 inhibition (≥80%) for18-20 hours after single and multiple-dose administration as compared to Galvus® (12-13 hours).Conclusions: Investigational vildagliptin SR tablet was found safe, well-tolerated after single and multiple-dose administration. Its extended DPP-4 inhibition profile compared to Galvus® may benefit the patient population on combination therapy with a sulphonylurea and renally impaired patients.

Comparative Clinical Pharmacokinetics and Pharmacodynamics of Investigational Once-Daily Sustained-Release (SR) Vildagliptin 100 mg Tablet Formulation with Conventional 50 mg Twice-Daily Regimen in Healthy Indian Males

“…Therefore, we explored OSMO laser technology to develop an SR vildagliptin tablet formulation of 100 mg strength for OD administration. Using a similar technology platform, earlier we successfully formulated a 50 mg SR vildagliptin tablet to achieve extended DPP-4 inhibition coverage in combination therapy [19]. Osmosis-mediated oral drug formulations are known to maintain sustained therapeutic levels of plasma drug concentrations for a longer interval without peak-to-trough fluctuations.…”

“…PD profiles of both the treatment cohorts were determined by estimating plasma DPP-4 inhibition activity in a previously established assay method [17][18][19]. This fluorescence-based enzymatic assay utilised Gly-Pro-7 amido-4-methylcoumarin hydrobromide (Sigma- Aldrich, MO, USA) as a substrate.…”

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

“…5 Utilizing the polymer matrix SR coating, Vildagliptin SR 100 mg tablet formulation was developed, allowing a once-daily (OD) administration. 6 This can be a practical therapeutic alternative to the twice-daily Vildagliptin IR 50 mg dose.…”