D. Kim,1 S. Lee,1 J. Choi,1 J. Ha,1 Y. Noh,2 J. Shin,2 J. Ghim2; 1Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine, Busan, Korea, Republic of, 2Department of Pharmacology and PharmacoGenomics Research Center, Inje University College of Medicine; Department of Clinical Pharmacology, Inje University Busan Paik Hospital, Busan, Korea, Republic of
BACKGROUND: Atorvastatin and metformin are indicated for hyperlipidemia and diabetes, respectively. As hyperlipidemia is a common comorbidity of diabetes, the two drugs are frequently prescribed in combination. The aim of this study was to evaluate the effect of a high-fat meal on the pharmacokinetic and safety profiles of a newly developed fixed dose combination (FDC) of atorvastatin/metformin XR 20/500 mg in healthy Korean subjects.
METHODS: This was a randomized, open-label, single-dose, two-way, crossover study. 28 eligible subjects, aged 20 to 50 years and within 20% of the ideal body weight, were enrolled. Each subject received a single dose FDC tablet of atorvastatin/metformin XR 20/500 mg 2 tablets in fasting or fed state. The two periods were separated by 1-week washout period. After the dose, blood samples were collected until 36 hours and 24 hours for atorvastatin and metformin, respectively. Adverse events (AEs) were evaluated based on subject interviews, physical examinations and laboratory tests.
RESULTS: A total of 27 subjects completed the study. The geometric mean ratios (90% confidence intervals) of the Cmax and AUC0-t were 0.6790 (0.5909-0.7803) and 0.9963 (0.9313-1.0658) for atorvastatin and 1.0260 (0.9418-1.1178) and 1.5556 (1.4345-1.6870) for metformin, respectively. Overall, one mild AE (headache) occurred in 27 subjects, with no significant difference in the incidence between the treatments.
CONCLUSION: The geometric mean Cmax of atorvastatin decreased by 67.9% (p<.0001) and the geometric mean AUC0-t of metformin increased by 155% (p<.0001) by the high-fat meal. All treatments were well tolerated, and no serious AEs occurred.