Journal of Bioequivalence & Bioavailability

Abstract

Bioequivalence Study of Dapagliflozin 10 mg Film Coated Tablets in Healthy Indonesian Subjects under Fasting Condition

Raymond R. Tjandrawinata*, Lucia Rat Handayani, Danang Agung Yunaidi, Vicky Achmad Ginanjar, Liana W. Susanto and Clarasintha Nindyatami

Purpose: This study aimed to demonstrate the bioequivalence of the Dapagliflozin 10 mg film-coated tablets manufactured by PT Dexa Medica, Indonesia, in comparison with the reference formulation, Forxiga^® 10 mg filmcoated tablets, manufactured by AstraZeneca Pharmaceuticals.

Patients and methods: This was an open-label, randomized, single-dose, two-period, two-sequence, two-way crossover study under fasting conditions with a 5-day washout period. 24 enrolled healthy subjects, 22 subjects completed the study. The test or reference formulation was administered orally to the subjects in a randomized manner. A validated Ultra-Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC-MS/MS) detection method was used to assay the plasma concentration of Dapagliflozin. This study assessed the following pharmacokinetic parameters: AUC_0–t, AUC_0–∞, C_max, t_max, and t_½. Bioequivalence was established in the Test/Reference Geometric Means Ratio (GMR), and the 90% Confidence Interval (CI) of GMR was between 80.00% and 125.00% with 0.05 alpha for AUC_0-t and C_max.

Results: The test dapagliflozin formulation had the mean ± Standard Deviation (SD) Cmax, AUC_0–t, AUC_0–∞, and t_1/2 values of 83.07 ± 30.34 ng/mL, 601.72 ± 174.46 ng ⋅ h/mL, 620.87 ± 180.38 ng ⋅ h/mL, and 10.50 ± 2.64 hours, respectively. For Dapagliflozin from the reference formulation, the mean ± SD for Cmax, AUC0–t, AUC0–∞, and t1/2 of were 80.29 ± 17.92 ng/mL, 606.64 ± 176.24 ng ⋅ h/mL, 626.15 ± 182.05 ng ⋅ h/mL, and 10.53 ± 2.69 hours, respectively. Dapagliflozin’s median (range) t_max was 2.00 (0.5-8.00) hours for the test formulation and 2.00 (1.00- 6.00) hours for the reference formulation. The GMR (90% CI) of the Test/Reference formulation for Dapagliflozin was 100.89% (89.72%-113.46%) for C_max and 99.21% (96.47%-102.04%) for AUC_0–t. No adverse event was reported in the study.

Conclusion: The results demonstrated that both formulations of Dapagliflozin 10 mg film-coated tablets were bioequivalent and were well tolerated by the subjects.

Published Date: 2024-02-19; Received Date: 2024-01-17