关键词: 达格列净二甲双胍缓释片, 药代动力学, 生物等效性, 临床试验

Abstract:

AIM: To compare the bioavailability and bioequivalence of dapagliflozin and metformin extended-release tablets in healthy Chinese subjects. METHODS: Plasma concentrations of dapagliflozin and metformin were determined using HPLC-MS/MS. Bioequivalence was analyzed using WinNonlin software (version 8.2) and SAS 9.4. RESULTS: Fasting conditions: After a single oral dose of the test or reference formulation (10 mg/1 000 mg dapagliflozin/metformin ER), the geometric mean ratios (90% confidence intervals) for dapagliflozin were C_max: 109.18% (101.89%-116.99%); AUC_0–t: 102.17% (99.37%-105.04%); AUC_0–∞: 101.92% (98.94%-104.99%). For metformin the values were C_max: 101.85% (96.67%-107.30%); AUC_0–t: 100.51% (95.36%-105.95%); AUC_0–∞: 100.03% (94.94%-105.39%). Fed conditions: After a single oral dose of the test or reference formulation, the geometric mean ratios (90% confidence intervals) for dapagliflozin were C_max: 98.27% (88.80%-108.74%), AUC_0–t: 103.09% (99.17%-107.16%); AUC_0–∞: 103.27% (99.25%-107.45%). For metformin, the values were C_max: 101.81% (98.36%-105.38%), AUC_0–t: 98.99% (94.45%-103.75%), AUC_0–∞: 98.94%(94.48%-103.61%). CONCLUSION: The two formulations are bioequivalent under both fasting and fed conditions.

Key words: dapagliflozin-metformin extended-release tablets, pharmacokinetics, bioequivalence, clinical trial