Topical anti-inflammatory properties of flutrimazole, a new imidazole antifungal agent.
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.
Merlos
M
M
Research Center, J. Uriach & Cía, Barcelona, Spain.
Vericat
M L
ML
García-Rafanell
J
J
Forn
J
J
D000287:Administration, Topical; D000818:Animals; D000875:Anthralin; D000893:Anti-Inflammatory Agents; D000935:Antifungal Agents / Q000627:therapeutic use*; D016718:Arachidonic Acid; D002351:Carrageenan; D003022:Clotrimazole / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000627:therapeutic use; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D006098:Granulocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007654:Ketoconazole / Q000494:pharmacology / Q000627:therapeutic use; D007975:Leukotriene B4 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D013755:Tetradecanoylphorbol Acetate
D000893:Anti-Inflammatory Agents; D000935:Antifungal Agents; D016861:Cyclooxygenase Inhibitors; D004008:Diclofenac; D007975:Leukotriene B4; D016718:Arachidonic Acid; C076986:flutrimazole; D002351:Carrageenan; D003022:Clotrimazole; D013755:Tetradecanoylphorbol Acetate; D007654:Ketoconazole; D000875:Anthralin