Topical anti-inflammatory effect of hypocholesterolaemic drugs.

Objectives: The topical anti-inflammatory effect of simvastatin, atorvastatin, pravastatin, ezetimibe and combined ezetimibe + simvastatin was investigated, using the croton oil model of ear oedema in mice.

Methods: Simvastatin, atorvastatin, pravastatin, ezetimibe and ezetimibe + simvastatin combination (dissolved in 20 µl of 70% acetone) were topically applied simultaneously with croton oil (200 µg/ear, dissolved in 20 µl of 70% acetone) at the inner surface of each ear. Ear oedema and myeloperoxidase activity, indicative of polymorphonuclear cell migration, were assessed 6 h after inflammatory stimuli.

Key Findings: It was found that statins can act as topical anti-inflammatories, but the pharmacological effect is dependent on statin polarity. At 0.3 mg/ear inhibition of ear oedema was 79%, 67% and 40% for simvastatin, atorvastatin and pravastatin, respectively. Simvastatin and atorvastatin also remarkably diminished myeloperoxidase activity, even at low concentrations (0.03 mg/ear). Pravastatin, the most polar statin, however, did not cause any reduction in ear oedema or myeloperoxidase activity at low doses. The order of topical anti-inflammatory activity was pravastatin < < < atorvastatin ≤ simvastatin. Ezetimibe, another hypocholesterolaemic drug, also presented anti-inflammatory effects, inhibiting ear oedema by 64% at 0.3 mg/ear. However, when used in combination with simvastatin, no further beneficial effect was observed.

Conclusions: These results consistently support current evidence showing that statins can be used for treatment of dermatological disorders. Polarity of the molecule, however, is a factor that should be considered before recommending use.