Back to Journals » Drug Design, Development and Therapy » Volume 11

Pharmacokinetic and pharmacodynamic interaction between ezetimibe and rosuvastatin in healthy male subjects

Authors Kim CH, An H, Kim SH, Shin D

Received 20 July 2017

Accepted for publication 7 November 2017

Published 5 December 2017 Volume 2017:11 Pages 3461—3469


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Tuo Deng

Chang Hee Kim,1 Hyungmi An,2 Sung Hye Kim,3 Dongseong Shin4

1Department of Urology, Gachon University Gil Medical Center, Incheon, 2Department of Statistics, Seoul National University, Seoul, 3Clinical Development, Navipharm Co., Ltd., Suwon, 4Clinical Trials Center, Gachon University Gil Medical Center, Incheon, South Korea

Background and objective: Rosuvastatin and ezetimibe are commonly applied in lipid-lowering pharmacotherapy. However, the pharmacokinetic (PK) interaction was not clear by the coadministration of rosuvastatin and ezetimibe. This study investigated the pharmacodynamic (PD) and PK interactions between rosuvastatin and ezetimibe through a crossover clinical trial.
Subjects and methods: A randomized, open-label, multiple-dose, two-treatment, two-period, two-sequence crossover study with two treatment parts was conducted in healthy male subjects. Study part A involved rosuvastatin, and study part B involved ezetimibe. A total of 25 subjects in both parts completed the PK and PD evaluations. Rosuvastatin (20 mg) or ezetimibe (10 mg) was administered once daily for 7 days as monotherapy or co-therapy. The plasma concentrations of rosuvastatin, total ezetimibe and free ezetimibe were measured for 72 h after day 7. Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC) were investigated for the PD assessments on day 1 (pretreatment) and day 8.
Results: Rosuvastatin and ezetimibe presented multiple peaks. The 90% confidence intervals (CIs) of the geometric mean ratios for the peak plasma concentration at steady state (Cmax,ss) and area under the plasma concentration–time curve during the dosing interval at steady state (AUCt,ss) of rosuvastatin and total ezetimibe were within the range 0.8–1.25. However, the coadministration increased the systemic exposure of free ezetimibe. In the PD assessments, rosuvastatin and ezetimibe monotherapy reduced the LDL-C and TC levels effectively. In addition, the lipid-lowering effects of the coadministration corresponded to an approximate summation of the effects of rosuvastatin and ezetimibe monotherapy. However, no significant changes in HDL-C were observed with rosuvastatin or ezetimibe treatment. No significant safety issue was noted.
Conclusion: The coadministration of rosuvastatin and ezetimibe revealed a bioequivalent PK interaction. Additional lipid-lowering effects, including decreased LDL-C and TC, were observed as expected in combination therapy without significant safety concern.

Keywords: pharmacokinetics, pharmacodynamics, drug interaction, rosuvastatin, ezetimibe

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]