H. Choi,1 D. Kim,1 J. Seo,1 J. Ghim,2 Y. Koo,1 J. Shin,1 E. Kim,2 E. Kim3; 1Inje University College of Medicine, Busan, Korea, Republic of, 2Inje University Busan Paik Hospital, Busan, Korea, Republic of, 3CJ HealthCare Crop., Seoul, Korea, Republic of
BACKGROUND: Metformin, an oral anti-hyperglycemic agent, and atorvastatin, a cholesterol-lowering agent, are frequently co-administered owing to the high comorbidity of hyperlipidemia with diabetes mellitus. The aim of this study was to investigate the pharmacokinetic interaction between the two drugs in healthy Korean male volunteers.
METHODS: A randomized, two-part, open-label, fixed sequence, one-way interaction study was conducted on healthy Korean subjects (aged 20 to 55 years). In part A, 60 subjects received atorvastatin 40 mg once daily for 7 days. After a 14-day washout period, atorvastatin 40 mg was dosed with metformin XR 1000 mg once daily for 7 days. In part B, 20 subjects received metformin XR 1000 mg once daily for 7 days. After a 7-day washout period, metformin XR 1000 mg was dosed with atorvastatin 40 mg once daily for 7 days. Blood samples were collected up to 36 h and 24 h for atorvastatin and metformin, respectively. Adverse events (AEs) were evaluated based on subject interviews, physical examinations and laboratory tests.
RESULTS: Among the 80 enrolled subjects, 50 in part A and 16 in part B completed the study. For atorvastatin, the geometric mean ratios (GMRs) (90% confidence intervals) of the Cmax,ss and AUCtau,ss were 1.0739 (0.9442-1.2214) and 1.0460 (0.9917-1.1032), respectively. For metformin, the GMRs (90% confidence intervals) of the Cmax,ss and AUCtau,ss were 1.0094 (0.8639-1.1795) and 0.9900 (0.8679-1.1292), respectively. Overall, 17 mild, 3 moderate, and 1 severe AEs occurred in 80 subjects, with no significant difference in the incidence between the treatments in each part.
CONCLUSION: There was no significant pharmacokinetic interaction when atorvastatin and metformin were co-administered. All treatments were well-tolerated, and no serious AEs occurred.