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Abstract
Purpose:
The aims of this study was to investigate the mutual pharmacokinetic interactions between steady-state atorvastatin and metformin and the effect of food on the fixed-dose combined (FDC) tablet of atorvastatin and metformin extended release (XR).
Subjects and methods:
Study 1, an open-labeled, fixed sequence, multiple-dose pharmacokinetic drug-drug interaction study, was divided into 2 parts. Atorvastatin (40 mg) or metformin (1,000 mg) XR tablets were administered once daily via mono- or co-therapy for 7 days. Plasma levels of atorvastatin and 2-OH-atorvastatin, were quantitatively determined for 36 h in part A (n=50) while metformin plasma concentration was measured up to 24 h in part B (n=16) after the last dosing. Study 2, a randomized, open-labeled, single-dose, two-treatment, two-period, two-sequence crossover study, involved 27 healthy subjects to investigate the impact of food intake on the pharmacokinetics of a combined atorvastatin/metformin XR 20/500 mg (CJ-30056 20/500 mg) tablet.
Results:
After multiple doses of mono- or co-therapy of atorvastatin (40 mg) and metformin (1,000 mg) XR, the 90% confidence intervals (CIs) of the geometric mean ratios (GMRs) for the peak plasma concentration at steady state (Cmax,ss) and area under the plasma concentration–time curve during the dosing interval at steady state (AUCτ,ss) were 1.07 (0.94–1.22) and 1.05 (0.99–1.10) for atorvastatin, 1.06 (0.96–1.16) and 1.16 (1.10–1.21) for 2-OH-atorvastatin, and 1.00 (0.86–1.18) and 0.99 (0.87–1.13) for metformin, respectively. Food delayed time to reach maximum concentration (tmax), decreased atorvastatin Cmax by 32% with a GMR (90% CI) of 0.68 (0.59–0.78), and increased metformin AUCt by 56% with a GMR (90% CI) of 1.56 (1.43–1.69).
Conclusion:
No clinically relevant pharmacokinetic interaction was seen when atorvastatin was co-administered with metformin. Food appeared to change the absorption of atorvastatin and metformin from an FDC formulation. These alterations were in accordance with those described with the single reference drugs when ingested with food.
Acknowledgments
This study was conducted with support by CJ HealthCare (Seoul, Republic of Korea), and we thank all clinical trial staff members for their contributions to this study.
Data sharing
Whether the authors intend to share individual deidentified participant data? No.
What specific data they intend to share? Not available.
What other study-related documents will be made available? Not available.
How the data will be accessible? Not applicable.
When and for how long they will be made available? Not applicable.
Disclosure
Eun-Ji Kim and Geun Seog Song are employees of CJ HealthCare (Seoul, Republic of Korea). Eun-Ji Kim reports a patent 10-1397343-0000; Geun Seog Song reports a patent 10-1397343-0000. Jae-Gook Shin report grants from a contracted clinical trial, outside the submitted work. The authors report no other conflicts of interest in this work.