109: Pharmacokinetic Comparison Between Fixed-dose Combination of Rosuvastatin/Ezetimibe 2.5/10 mg & the Coadministration of Individual Formulations in Healthy Subjects

Statement of Purpose, Innovation or Hypothesis: The combination therapy of low-dose rosuvastatin and ezetimibe has shown similar efficacy in decreasing low-density lipoprotein cholesterol (LDL-C) compared to high-dose rosuvastatin monotherapy. This study aimed to compare the pharmacokinetics (PK) between the fixed-dose combination (FDC) of rosuvastatin/ezetimibe 2.5/10 mg and the coadministration of individual formulations.

Description of Methods & Materials: A randomized, open-label, single-dose, 2-sequence, 2-period, crossover study was conducted in healthy volunteers. Subjects were randomized in each sequence and received a single dose of FDC of rosuvastatin/ezetimibe 2.5/10 mg or the coadministration of individual formulations in each period with a 14-day washout. Serial blood samples for PK analysis were collected up to 48 hours post-dose for rosuvastatin and 72 hours post-dose for ezetimibe. The geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of the FDC to the coadministration each formulation for maximum plasma concentration (C_max) and area under the curve from zero to the last measurable time point (AUC_last) were calculated. Safety and tolerability were evaluated by monitoring adverse events (AEs), physical examination, vital sign, 12-lead electrocardiogram, and clinical laboratory test throughout the study.

Data & Results: Forty-seven subjects were randomized, and 41 subjects completed the study. The GMRs (90% CIs) of C_max and AUC_last for rosuvastatin were 0.9789 (0.9020–1.0622) and 0.9741 (0.9105–1.0422). The corresponding values were 1.0419 (0.9219–1.1776) and 0.9983 (0.9522–1.0465) for total ezetimibe, and 1.0396 (0.9087–1.1893) and 0.9743 (0.8997–1.0550) for free ezetimibe, respectively. All the values were within the conventional bioequivalence criteria of 0.8 to 1.25. Both FDC and coadministration of individual formulations were well tolerated.

Interpretation, Conclusion or Significance: The FDC of rosuvastatin/ezetimibe 2.5/10 mg showed comparable PK characteristics with the coadministration of individual formulations.

Disclosures: This study was sponsored by Addpharma Pharmaceutical Corp., Korea. The authors do not have any conflicts of interest in this study.

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