S. Seong, J. Lee, S. Park, M. Gwon, H. Kim, H. Lee, Y. Yoon; Kyungpook National University Hospital Clinical Trial Center, Daegu, Korea, Republic of
BACKGROUND: Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has been used for the management of dyslipidemia. Ezetimibe is a lipid lowering agent by inhibiting of intestinal cholesterol absorption. A new combination tablet of rosuvastain and ezetimibe has been developed to reduce pill burden and improve adherence. This study was designed to investigate and compare the pharmacokinetic properties of a fixed-dose combination (FDC) tablet of rosuvastatin and ezetimibe with concomitant administration of individual agents.
METHODS: A randomized, open-label, single-dose, two-period, two-way crossover study with washout periods of 14 days was performed. 40 healthy male participants were allocated to receive a single dose of the combination tablet of rosuvastatin 10 mg and ezetimibe 10 mg or coadministration of two individual agents. Plasma samples were taken for 96 hours after dosing for determination of drug concentration. Plasma drug concentrations were analyzed using a validated liquid chromatography coupled with tandem mass spectrometry. The safety profiles were also investigated based on adverse events, clinical laboratory tests, and reporting by subjects.
RESULTS: The 90% CIs of the geometric mean ratios of the FDC to the individual agents for Cmax and AUClast of rosuvastatin were 0.97-1.17 and 0.96-1.10, respectively. The 90% CIs for ezetimibe for Cmax and AUClast were 0.99-1.21 and 0.92-1.05, respectively. Both treatments were safe and well tolerated throughout the study.
CONCLUSION: Rosuvastatin/ezetimibe FDC tablet was bioequivalent to the concomitant administration of individual rosuvastatin and ezetimibe tablet.