PII-069 - PHARMACOKINETIC COMPARISON BETWEEN A FIXED-DOSE COMBINATION OF ATORVASTATIN/OMEGA-3 AND THE CORRESPONDING LOOSE COMBINATION IN HEALTHY KOREAN SUBJECTS.

J. Khwarg¹, S. Lee¹, J. Oh², W. Kang³, H. Lee⁴, K. Kim⁴, K. Jeong⁴, C. Won⁴, Y. Choi³, D. Ha³, R. Jung³, M. Han³, W. Jung³, K. Nam³, Y. Kim³, I. Jang²; ¹Seoul National University Bundang Hospital, Seoul, Republic of Korea, ²Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea, ³Korea United Pharm., Inc., Seoul, Republic of Korea, ⁴Caleb Multilab., Inc., Seoul, Republic of Korea.

Background: A combination treatment of statin and omega-3 is widely used in patients with combined hyperlipidemia (CHL). The aim of this study was to compare the pharmacokinetic (PK) profile of atorvastatin and omega-3 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 received four FDC soft capsules of atorvastatin/omega-3 ethyl esters (10/1000 mg) or loose combination of atorvastatin tablet (10 mg × 4) and omega-3 ethyl esters soft capsule (1000 mg× 4) with a high-fat meal in each period. 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. Geometric mean ratio (GMR) and it’s 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.

Conclusion: The FDC of atorvastatin and omega-3 showed comparable PK characteristics to the corresponding loose combination, offering a convenient therapeutic option for the treatment of CHL.