© 2004 The International Society of Dermatology International Journal of Dermatology 2004, 43 (Suppl.1), 3 – 8 3 Blackwell Publishing, Ltd. Oxford, UK IJD International Journal of Dermatology 0011-9059 Blackwell Science, 2004 43 Suppl.: if known Original article Ciclopirox: antifungal, antibacterial and anti-inflammatory properties Ciclopirox: antifungal, antibacterial and anti-inflammatory properties Ciclopirox: a broad-spectrum antifungal with antibacterial and anti-inflammatory properties Aditya K. Gupta, MD, PhD, FRCP(C) 1,2 , and Todd Plott, MD 3 1 Division of Dermatology, Department of Medicine, Sunnybrook and Women’s College Health Science Center (Sunnybrook site) and the University of Toronto, Toronto, Canada; 2 Mediprobe Research Inc., London, Ontario, Canada; 3 Medicis Pharmaceutical Corporation, Scottsdale, Arizona Correspondence Aditya K. Gupta, MD, PhD, FRCP(C) Suite 6, 490 Wonderland Road South London Ontario Canada E-mail: agupta@execulink.com Introduction Ciclopirox is a synthetic agent available worldwide in a variety of formulations to treat superficial fungal and yeast infections, vaginal candidiasis, seborrheic dermatitis, and onychomy- cosis. In the USA, ciclopirox is available in five formulations to treat a variety of superficial mycoses including tinea pedis, tinea corporis/cruris, pityriasis (tinea) versicolor, and seborrheic dermatitis (Table 1). Ciclopirox 0.77% gel has been reported as a successful treatment for tinea pedis. 1,2 Ciclopirox 8% nail lacquer is indicated in the USA for the treatment of onychomy- cosis. The most recently approved formulation, ciclopirox shampoo 1%, is indicated for the treatment of seborrheic dermatitis of the scalp in adults, a condition in which Malas- sezia species are believed to play a role in pathogenesis. Ciclopirox is a hydroxypyridone derivative (Fig. 1), formed from the ethanolamine salt of 6- cyclohexyl-1-hydroxy-4- methyl-2(1H)-pyridone. 3 Ciclopirox olamine 1% is equivalent to 0.77% of the free acid form (ciclopirox 0.77%), and the olamine entity does not add to the antifungal effect. 3 The mechanism of action of ciclopirox differs from that of the azole, imidazole and allylamine antifungal agents. Furthermore, in addition to a broad-spectrum antifungal activity, ciclopirox has demonstrated broad-spectrum antibacterial activity and anti- inflammatory properties. Thus, ciclopirox has proven useful for a wide variety of superficial dermatoses, including those that involve bacterial infection and inflammation. Mechanism of action Azole, imidazole and allylamine antifungal agents produce anti- fungal actions by inhibiting enzymes involved in the production of fungal ergosterol, a required component of the fungal cell membranes. This inhibition may be fungistatic or fungicidal. Ciclopirox was found to inhibit the growth of dermato- phyte fungi, other nonpathogenic fungi, Candida albicans , Gram-positive and Gram-negative bacteria. 4–6 Studies in Can- dida albicans indicated that ciclopirox did not inhibit synthe- sis of the cell wall, but prevented incorporation of radioactive precursors into proteins, RNA and DNA. 4 Concentrations above 50 μ g/ml caused leakage of folin-positive substances (amino acids and peptides) and potassium ions from the C. albicans cells. High concentrations also appreciably inhibited oxidative use of glucose and other exogenous substrates by C. albicans , but did not affect endogenous respiration and there- fore interference with electron transport was not suspected to be the primary cause of antifungal activity. The drop in RNA, DNA and protein synthesis was suspected to result from blockage of transmembrane transport of precursors, rather than blockage of the assembly process, and therefore ciclopirox may alter cell permeability. Further study suggested that chelation of metal ions by ciclopirox may lead to inhibition of iron-dependent enzymes. 6,7 Using freeze-fracture technique and electron microscopy, an in vitro analysis demonstrated that ciclopirox modified the