https://orcid.org/0000-0001-7097-2006
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Abstract
Purpose
Statins are widely used in combination with omega-3 fatty acids for the treatment of patients with dyslipidemia. The aim of this study was to compare the pharmacokinetic (PK) profiles of atorvastatin and omega-3-acid ethyl esters between fixed-dose combination (FDC) and loose combination in healthy subjects.
Methods
A randomized, open-label, single-dose, 2-sequence, 2-treatment, 4-period replicated crossover study was performed. Subjects were randomly assigned to one of the 2 sequences and alternately received four FDC soft capsules of atorvastatin/omega-3-acid ethyl esters (10/1000 mg) or a loose combination of atorvastatin tablets (10 mg × 4) and omega-3-acid ethyl ester soft capsules (1000 mg× 4) for four periods, each period accompanied by a high-fat meal. Serial blood samples were collected for PK analysis of atorvastatin, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). PK parameters were calculated by a non-compartmental analysis. The geometric mean ratio (GMR) and its 90% confidence interval (CI) of the FDC to the loose combination were calculated to compare PK parameters.
Results
A total of 43 subjects completed the study as planned. The GMR (90% CI) of FDC to loose combination for maximum concentration (Cmax) and area under the time-concentration curve from zero to the last measurable point (AUClast) were 1.0931 (1.0054–1.1883) and 0.9885 (0.9588–1.0192) for atorvastatin, 0.9607 (0.9068–1.0178) and 0.9770 (0.9239–1.0331) for EPA, and 0.9961 (0.9127–1.0871) and 0.9634 (0.8830–1.0512) for DHA, respectively. The intra-subject variability for Cmax and AUClast of DHA was 30.8% and 37.5%, respectively, showing high variability. Both the FDC and the loose combination were safe and well tolerated.
Conclusion
The FDC of atorvastatin and omega-3-acid ethyl esters showed comparable PK characteristics to the corresponding loose combination, offering a convenient therapeutic option for the treatment of dyslipidemia.
Graphical Abstract
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Data Sharing Statement
The data supporting the published results of this study will be shared upon a reasonable request made to the corresponding author or sponsor.
Acknowledgment
Juyoung Khwarg received a scholarship from the BK21FOUR education program.
Disclosure
Won-Ho Kang, Youn Woong Choi, Dae Chul Ha, RaeHoon Jung, Min-Gu Han, Won Tae Jung, Kyu-Yeol Nam, and YeSeul Kim are employees of Korea United Pharm. Inc. Hye Jung Lee, Kyu Yeon Kim, Ki-Sun Jeong, and Chongho Won are employees of Caleb Multilab, Inc. The other authors do not have any conflicts of interest for this study.