1. Comparison of the Pharmacokinetics, Safety, and Tolerability of Two Empagliflozin Formulations in Healthy Korean Subjects.
- Author
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Jiang X, Bae S, Yoon DY, Park SJ, Oh J, Cho JY, and Yu KS
- Subjects
- Adult, Humans, Healthy Volunteers, Cross-Over Studies, Area Under Curve, Therapeutic Equivalency, Administration, Oral, Republic of Korea, Tablets, Diabetes Mellitus, Type 2 drug therapy, Renal Insufficiency, Chronic
- Abstract
Purpose: Empagliflozin is a sodium-glucose cotransporter 2 inhibitor that is commonly used for the treatment of type 2 diabetes mellitus. As cocrystal formulation can improve the chemical properties of drugs, CKD-370 was newly developed as a cocrystal formulation of empagliflozin with solvate L-proline. This study aimed to compare the pharmacokinetics, safety, and tolerability of these two empagliflozin formulations in healthy Korean subjects., Methods: A randomized, open-label, two-sequence, two-period crossover study was conducted on healthy Korean participants. The subjects received a single oral 25 mg dose of either test (CKD-370) or reference treatment (Jardiance
® ) tablet at each period. Plasma empagliflozin concentrations were determined using liquid chromatography with tandem mass spectrometry. Pharmacokinetic (PK) parameters were analyzed using non-compartmental methods. The primary PK parameters included the maximum concentration (Cmax ) and the area under the concentration-time curve from 0 to last (AUClast ). The safety of both formulations was monitored and evaluated., Results: A total of 28 healthy Korean adult subjects were randomized, and 27 subjects were included in the PK analysis. The mean ± standard deviation values of the primary PK parameters, Cmax and AUClast after administration of the test treatment, were 442.02 ± 103.37 μg/L and 3131.08 ± 529.30 μg·h/L, respectively, and those after administration of the reference treatment were 436.29 ± 118.74 μg/L and 3006.88 ± 514.21 μg·h/L, respectively. The geometric mean ratio and its 90% confidence interval of test to reference treatment for Cmax and AUClast were 1.0221 (0.9527-1.0967) and 1.0411 (1.0153-1.0677), respectively, which were within the commonly accepted bioequivalence criteria of 0.80 to 1.25. Both treatments were well-tolerated., Conclusion: The two formulations of empagliflozin showed similar PK characteristics and were generally well tolerated in healthy subjects., Competing Interests: Shin Jung Park is a full-time employee of Chong Kun Dang Pharmaceutical Corporation. The authors report no other conflicts of interest associated with this work., (© 2023 Jiang et al.)- Published
- 2023
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