Could simvastatin be considered as a potential therapy for chronic lung diseases? A debate on the pros and cons

ABSTRACT

Introduction: Simvastatin (SV) is a drug from the statin class, currently used orally as an anti-cholesterolemic drug. It inhibits the 3-hydroxy-3-methyl-glutaryl-Coenzyme A (HMG-CoA) reductase to reduce cholesterol synthesis. Recently, it has been found that SV also has several other protective pharmacological actions unrelated to its anti-cholesterol effects that might be beneficial in the treatment of chronic airway diseases.

Areas covered: This review summarizes the evidence relating to SV as a potential anti-inflammatory, anti-oxidant and muco-inhibitory agent, administered both orally and via pulmonary inhalation, and discusses its pro and cons. Evidence could potentially be used to support the delivery of SV as inhaled formulation for the treatment of chronic respiratory diseases.

Expert opinion: The use of SV as anti-inflammatory, anti-oxidant and muco-inhibitory agent for drug delivery to the lung is promising. Inhaled SV formulations could allow the delivery profile to be customized and optimized to take advantage of the rapid onset of action, low systemic side effect and improved physico-chemical stability. This treatment could potentially to be used clinically for the localized treatment of lung diseases where inflammation and oxidative stress production is present.

KEYWORDS:

• Simvastatin
• anti-inflammatory
• anti-oxidant
• muco-inhibitory
• stability
• respiratory diseases

Article highlights

• By 2020, chronic lung diseases will become the 3^rd leading cause of death.

• Reformulating an established oral drug, such as simvastatin, could become an alternative solution or adjunct new therapy for the treatment of inflammatory diseases in the lung.

• Simvastatin has other possible pleiotropic effects beside it lowering cholesterol properties. However, the full benefit of oral simvastatin therapeutic value is hampered by the low stability and water solubility, resulting in low bioavailability in vivo.

• Simvastatin is chemically metabolized into the active form of simvastatin hydroxy acid (SVA). Hence, SV has to be delivered in its pro-drug form.

• Both in vitro and in vivo studies demonstrated that administration of simvastatin has anti-inflammatory, anti-oxidant, muco-inhibitor and anti-proliferative effects that could be used to treat lung diseases.

• Inhaled formulations of simvastatin (e.g. DPI and pMDI) could overcome its stability issue, low bioavailability and directly deliver the drug to the site of action.

This box summarizes key points contained in the article.

Declaration of interest

Alaa Tulbah is appreciative to Umm Al-Qura University for the Scholarship and the Saudi Government for its financial support. Professor Young is the recipient of an Australian Research Council Future Fellowship (project number FT110100996). Professor Traini is the recipient of an Australian Research Council Future Fellowship (project number FT12010063). The authors have no other 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 apart from those disclosed.