TOPICAL ANTIINFLAMMATORY PROPERTIES OF FLUTRIMAZOLE, A NEW IMIDAZOLE ANTIFUNGAL AGENT

The topical anti-inflammatory properties of flutrimazole, a new imidaz ole antifungal, have been evaluated. Flutrimazole inhibited mouse ear oedema induced by arachidonic acid, tetradecanoylphorbol-acetate and d ithranol, with IC50 values of 3.32, 0.55 and 2.42 mu mols/ear, respect ively. Ketoconazole showed similar potency in arachidonic acid and dit hranol models (IC50 = 3.76 and 2.41 mu mols/ear) whereas it was less a ctive against tetradecanoylphorbol acetate (IC50 = 1.96 mu mols/ear). The standard anti-inflammatory sodium diclofenac was overall slightly more (IC50 = 2.23, 0.57 and 0.57 mu mols/ear against arachidonic acid, tetradecanoylphorbol acetate and dithranol, respectively). Both 2% fl utrimazole and 2% ketoconazole creams, applied topically, inhibited ca rrageenan-induced rat paw oedema by about 40%. Under the same conditio ns, 1% flutrimazole and diclofenac creams inhibited by 26 and 54%, res pectively. Flutrimazole may work through the inhibition of 5-lipoxygen ase, as it inhibited LTB(4) production by human granulocytes with an I C50 value of 11 mu M (IC50 value for ketoconazole was 17 mu M), wherea s ram seminal vesicle cyclooxygenase was only inhibited by 16% at a co ncentration of 25 mu M. Drugs such as flutrimazole, with dual anti-inf lammatory/antifungal activity, may be advantageous in the treatment of topical fungal infections with an inflammatory component.