Pharmacokinetic comparison between the fixed-dose combination of rosuvastatin/ezetimibe 2.5/10 mg and the co-administration of individual formulations in healthy subjects.

UNLABELLED

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 (PKs) between the fixed-dose combination (FDC) of rosuvastatin/ezetimibe 2.5/10 mg and the co-administration of individual formulations. 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 the FDC of rosuvastatin/ezetimibe 2.5/10 mg or the co-administration 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 co-administration for maximum plasma concentration (C) and area under the curve from zero to the last measurable time point (AUC) were calculated. Forty-seven subjects were randomized, and 41 subjects completed the study. The GMRs (90% CIs) of C and AUC 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. In conclusion, the FDC of rosuvastatin/ezetimibe 2.5/10 mg showed comparable PK with the co-administration of individual formulations.

TRIAL REGISTRATION

Clinical Research Information Service Identifier: KCT0009254.