Pharmacokinetic Interactions and Tolerability of Rosuvastatin and Ezetimibe: A Randomized, Phase 1, Crossover Study in Healthy Chinese Participants

Background and Objective The combination of rosuvastatin and ezetimibe has promising clinical benefits with a significant safety and tolerability profile. However, there is a lack of clinical data supporting the drug–drug interaction (DDI) in Chinese population. Thus, the aim of this study is to assess the potential pharmacokinetic DDI between rosuvastatin and ezetimibe in a Chinese population. Methods In this randomized, open-label, phase 1 study, 12 healthy volunteers were randomized to three treatment groups: 10 mg rosuvastatin plus 10 mg ezetimibe, 10 mg rosuvastatin alone, and 10 mg ezetimibe alone under fasting conditions. The plasma concentrations of rosuvastatin and ezetimibe were determined, and the pharmacokinetic parameters were calculated. Primary endpoints were peak plasma concentration ( C max ), area under the curve from zero to last measurement (AUC 0–t ), and area under the curve from zero to infinity (AUC 0–∞ ) that were log-transformed, and co-administration was compared with monotherapy to evaluate the DDI. Results The geometric mean ratios (GMRs) of rosuvastatin with 90% confidence intervals (CIs) were 0.94 (0.80–1.12) for C max , 0.96 (0.85–1.08) for AUC 0–t , and 0.96 (0.86–1.07) for AUC 0–∞ when administered in combination with ezetimibe versus administered alone. The GMRs of unconjugated ezetimibe and total ezetimibe with 90% CIs were 1.15 (1.00–1.32) and 0.93 (0.80–1.07) for C max , 0.96 (0.84–1.10) and 0.95 (0.83–1.08) for AUC 0–t , and 1.06 (0.96–1.18) and 0.94 (0.80–1.11) for AUC 0–∞ , respectively, when administered in combination with rosuvastatin versus administered alone. Conclusion Co-administration of rosuvastatin and ezetimibe showed no clinically significant pharmacokinetic interactions in a healthy Chinese population.