Pharmacokinetics and bioequivalence of a rosuvastatin/ezetimibe fixed-dose combination tablet versus single agents in healthy male subjects

Objective: The pharmacokinetic profiles and bioequivalence of a new rosuvastatin/ezetimibe fixed-dose combination (FDC; NVP-1205) vs. rosuvastatin and ezetimibe concomitantly administered as single agents were evaluated. Materials and methods: In this open-label, single-dose, crossover study (NCT02029625), eligible subjects were randomly assigned in a 1 : 1 ratio to receive a single dose of rosuvastatin (10 mg) with ezetimibe (10 mg) as either a FDC or as single agents concomitantly administered under fasted conditions, followed by a 2-week washout period and administration of the alternate formulation. Serial blood samples were collected predose and up to 96 hours postdose in each period for determination of plasma rosuvastatin and ezetimibe concentrations by liquid-chromatography tandem mass spectroscopy and calculation of pharmacokinetic parameters. Results: The mean C-max and AUC(0-t) values of rosuvastatin were 12.5 ng/mL and 115.6 ngxh/mL for the FDC, and 12.2 ng/mL and 115.1 ngxh/mL for the single agents concomitantly administered, respectively. The mean C-max and AUC(0-t) values of ezetimibe were 4.7 ng/mL and 67.3 ngxh/mL for the FDC, and 4.5 ng/mL and 68.2 ngxh/mL for the single agents concomitantly administered, respectively. The geometric mean ratio (GMR) and 90% confidence interval (CI) for the rosuvastatin C-max and AUC(0-t) were 106.20 (96.62 - 116.74) and 102.88 (96.32 - 109.90), respectively. The GMR and 90% CI for the ezetimibe C-max and AUC(0-t) were 108.96 (98.56 - 120.51) and 98.13 (92.01 - 104.66), respectively. All treatments were well tolerated during this study, with no serious adverse events reported. Conclusion: The rosuvastatin/ezetimibe (10/10 mg) FDC was bioequivalent to single agents concomitantly administered. A single dose of rosuvastatin/ezetimibe as the FDC or as single agents was well tolerated.