Comparison of Pharmacokinetics and Safety of a Fixed-dose Combination of Rosuvastatin and Ezetimibe Versus Separate Tablets in Healthy Subjects

• Published in: Clinical therapeutics Vol. 39; no. 9; pp. 1799 - 1810
• Main Authors: Min, Kyoung Lok, Park, Min Soo, Jung, Jina, Chang, Min Jung, Kim, Choon Ok
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2017; Elsevier Limited
• Subjects: Cardiovascular disease; Cholesterol; Chronic illnesses; Clinical medicine; Drug dosages; ezetimibe; Family medical history; fixed-dose combination; Hypertension; Lipids; Low density lipoprotein; Metabolism; Pharmacokinetics; Review boards; rosuvastatin; Sample size; Statins; Tablets; pharmacokinetics; ezetimibe; fixed-dose combination; rosuvastatin
• ISSN: 0149-2918; 1879-114X; 1879-114X
• DOI: 10.1016/j.clinthera.2017.07.038

Rosuvastatin and ezetimibe are concomitantly used for dyslipidemia treatment. Compared with separate tablets, fixed-dose combination (FDC) tablets of rosuvastatin/ezetimibe could increase patient compliance. The aim of this study was to compare the pharmacokinetic (PK) profiles of an FDC tablet of rosuvastatin/ezetimibe and co-administration of rosuvastatin and ezetimibe as separate tablets in healthy Korean volunteers. This trial was a randomized, open-label, single-dose, 2-way crossover study. The healthy subjects received an FDC tablet of rosuvastatin 20 mg/ezetimibe 10 mg (test) or co-administration of rosuvastatin 20 mg and ezetimibe 10 mg (reference) in each period (periods 1 and 2), with a 14-day washout period. The blood samples for PK analysis were collected predose and up to 96 hours after administration, and safety was assessed throughout the study. Sixty-four healthy Korean subjects were enrolled, and 57 subjects completed the study. All subjects were men and mean age was 28.52 ± 5.93. The geometric least squares mean ratios (test/reference) and 90% CIs of Cmax and AUC0–last were 101.54% (94.03–109.65) and 97.71% (91.86–103.93) for rosuvastatin, 108.93% (98.55–120.40) and 102.90% (96.72–109.47) for free ezetimibe, and 106.74% (98.18–116.05) and 104.24 % (99.53–109.17) for total ezetimibe. Twenty-four adverse events (AEs) were reported in 22 subjects. Three cases were related to the study drugs; 2 cases were mild, and 1 case was severe. However, all AEs were resolved without any sequelae. In addition, there were no serious AEs throughout the study. The FDC tablet of rosuvastatin/ezetimibe was well tolerated and resulted in comparable systemic exposure with co-administration of rosuvastatin and ezetimibe. ClinicalTrials.gov identifier: NCT02941848.