Objective: The aim of the present study was to evaluate the relative bioavailability of two formulations containing 10 mg dapagliflozin in healthy Caucasian subjects under fasting conditions.
Materials and Methods: Forty-eight healthy Caucasian subjects were enrolled in a single-dose, crossover, balanced, open label, randomized clinical trial, with two treatment, two periods and two sequences. The wash-out period was of 7 days and thirty-eight subjects completed both study periods. Each subject received a single dose of 10 mg dapagliflozin as the reference product Farxiga® (AstraZeneca Pharmaceuticals LP, USA) and the test product developed by Sun Pharmaceutical Industries, India. Dapagliflozin plasma levels were determined from blood samples collected in both study periods before and after dosing until 48 hours by using a validated LC-MS/MS method. For pharmacokinetic analysis of data, the non-compartmental method was used (Phoenix® WinNonlin 6.3). The statistical analysis was performed by SAS software 9.1.3 for the logarithmically transformed values of maximum plasma concentration and area under the curve.
Results: The 90% confidence intervals for the evaluated pharmacokinetic parameters were found to be in the accepted interval for bioequivalence (80.00-125.00%).
Conclusion: The 10 mg dapagliflozin immediate release tablet newly developed by Sun Pharmaceutical Industries, India, is bioequivalent with the reference product Farxiga® under fasted state of the subjects.
2. Pop DI, Oroian M, Bhardwaj S, Marcovici A, Khuroo A, Kochhar R, Vlase L. Bioequivalence of two formulations of gliclazide in a randomized crossover study in healthy Caucasian subjects under fed condition. Farmacia 2018; 66(4): 597-601.
4. Pop DI, Oroian M, Bhardwaj S, Marcovici A, Khuroo A, Kochhar R, Vlase L. Bioequivalence of two formulations of gliclazide in a randomized crossover study in healthy Caucasian subjects under fasting conditions. Clin Pharm Drug Dev 2019; 8(1): 16-21.
6. Pop DI, Gheldiu AM, Oroian M, Marcovici A, Bhardwaj S, Khuroo A, Kochhar R, Vlase L. Effect of food on the pharmacokinetics of gliclazide 60 mg modified release tablet in healthy Caucasian volunteers. Acta Med Marisiensis 2018; 64(4): 161-168.
9. Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: perspectives on the past, present and future. Lancet 2014; 383(9922): 1068–1083.
10. McGurnaghan SJ, Brierley L, Caparrotta TM et al. The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus: a real-world observational study. Diabetologia 2019; 62: 621-632.
11. Oroian M, Marcovici A, Pop DI, Bhardwaj S, Khuroo A, Gheldiu AM, Vlase L. Kinetics of dapagliflozin after single dose oral administration of a 10 mg immediate release tablet. Studia UBB Chemia 2019; LXIV(2, Tom I): 297-308.
12. List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009; 32(4): 650–657.
13. Henry RR, Rosenstock J, Edelman S et al. Exploring the potential of the SGLT2 inhibitor dapagliflozin in type 1 diabetes: a randomized, double-blind, placebo-controlled pilot study. Diabetes Care 2015; 38(3): 412–419.
14. Ferrannini E, Jimenez Ramos S, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise. Diabetes Care 2010; 33(10): 2217–2224.