Pharmacokinetic drug evaluation of ezetimibe + simvastatin for the treatment of hypercholesterolemia

ABSTRACT

Introduction: Cholesterol lowering treatment is mainly based on statins eventually associated to adjunctive drugs of different class such as ezetimibe. In the present review, we analysed the pharmacokinetics, efficacy and safety of ezetimibe + simvastatin drug association.

Areas covered: The bio-equivalence of ezetimibe and simvastatin when co-administrated in separate tablets or combined in a single pill is well documented. Ezetimibe is absorbed in small intestine, reaching peak plasma concentrations in 4–12 h, with a plasma half-life of 22 h. Simvastatin, ingested as a prodrug, is hydrolyzed in liver to its active beta-hydroxyacid metabolite, reaching peak plasma concentrations in 2–4 h, with a plasma half-life of approximately 5 h. The available evidence support the clinical efficacy of this drug combination, both in term of LDL-cholesterol reduction and cardiovascular risk decrease.

Expert opinion: The synergistic action of these two drugs and the efficacy and safety extensively demonstrated of their association (in particular in the large IMProved Reduction of Outcomes: Vytorin Efficacy International Trial -IMPROVE-IT-) promote its clinical use, especially in subjects with high cardiovascular risk who need to optimize their LDL-Cholesterolemia, but also in patients who cannot tolerate high-dose of more powerful statins.

KEYWORDS:

• Ezetimibe/simvastatin administration
• pharmacokinetics
• efficacy
• safety

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper is not funded.