Topical anti-inflammatory properties of flutrimazole, a new imidazole antifungal agent.

M Merlos, M L Vericat, J García-Rafanell, J Forn

Index: Inflamm. Res. 45(1) , 20-5, (1996)

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Abstract

The topical anti-inflammatory properties of flutrimazole, a new imidazole antifungal, have been evaluated. Flutrimazole inhibited mouse ear oedema induced by arachidonic acid, tetradecanoylphorbol-acetate and dithranol, with IC50 values of 3.32, 0.55 and 2.42 mumols/ear, respectively. Ketoconazole showed similar potency in arachidonic acid and dithranol models (IC50 = 3.76 and 2.41 mumols/ear) whereas it was less active against tetradecanoylphorbol acetate (IC50 = 1.96 mumols/ear). The standard anti-inflammatory sodium diclofenac was overall slightly more potent than antifungals (IC50 = 2.23, 0.57 and 0.57 mumols/ear against arachidonic acid, tetradecanoylphorbol acetate and dithranol, respectively). Both 2% flutrimazole and 2% ketoconazole creams, applied topically, inhibited carrageenan-induced rat paw oedema by about 40%. Under the same conditions, 1% flutrimazole and diclofenac creams inhibited by 26 and 54%, respectively. Flutrimazole may work through the inhibition of 5-lipoxygenase, as it inhibited LTB4 production by human granulocytes with an IC50 value of 11 microM (IC50 value for ketoconazole was 17 microM), whereas ram seminal vesicle cyclooxygenase was only inhibited by 16% at a concentration of 25 microM. Drugs such as flutrimazole, with dual anti-inflammatory/antifungal activity, may be advantageous in the treatment of topical fungal infections with an inflammatory component.