AstraZeneca presented the results of a Russian study on the bioequivalence of fixed and free combinations of dapagliflozin with metformin at the congress of the American Diabetes Association
June 11 at the Congress of the American Diabetes Association in the poster session presented the results of a Russian study of the company "AstraZeneca" on the bioequivalence of fixed and free combinations of dapagliflozin with metformin modified release.
An open randomized cross-over study (NCT02722239) compared the pharmacokinetics of a fixed combination of dapagliflozin and metformin modified release in tablets (10 mg + 1000 mg), compared with separate dapagliflozin intake in 10 mg tablets and sustained release metformin in two 500 mg tablets, at Russian healthy volunteers after eating.
40 healthy volunteers from Russia were randomized and completed the study. The pharmacokinetic parameters between the fixed combination and the intake of individual components were summarized and compared, including the area under the curve from the zero time to the last measurable concentration (AUC0-t), the maximum concentration in plasma (Cmax) and Cmax/ AUC0-t. For dapagliflozin, the calculated values of the 90% confidence interval (CI) of the AUC0-t, Cmax and Cmax/ AUC0-t were 95.94-102.33%, 87.89-102.19% and 89.10-102.68%, respectively. For metformin, the calculated values of the 90% CI of the AUC0-t, Cmax and Cmax/ AUC0-t amounted to 89.49-102.79%, 98.49-110.61% and 101.61-116.56% respectively.
For both dapagliflozin and metformin, 90% CI of AUC0-t, Cmax and Cmax/ AUC0-t for fixed combination and individual components are within the range of 80.00 - 125.00%,indicating a bioequivalence of a fixed combination of dapagliflozin with metformin modified release (10 mg + 1000 mg) and separate tablets. The interchangeability of the fixed combination and the intake of tablets was established separately. Fixed combinations of dapagliflozin and metformin could potentially become one of the new treatments for Type 2 diabetes mellitus, which improves adherence to treatment regimens by reducing the total number of tablets taken compared to alternative regimens suggesting their separate admission.