Ciclopirox

Abstract

Ciclopirox is a topical antimycotic agent belonging to the chemical class of hydroxypyridones and not related to azoles or any other class of antifungal agents. Its antimicrobial profile includes nearly all of the clinically relevant dermatophytes, yeasts and moulds, and is therefore broader than that of most other antimycotics. It is also active against certain frequently azole-resistant Candida species and against some bacteria. The mechanism of action of ciclopirox is different from that of other topical antifungal drugs, which generally act through ergosterol inhibition. The high affinity of ciclopirox for trivalent metal cations, resulting in inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell, appears to be the major determinant of its antimicrobial activity. This unique and multilevel mechanism of action provides a very low potential for the development of resistance in pathogenic fungi, with cases of resistance rarely reported. Ciclopirox also displays mild anti-inflammatory effects in biochemical and pharmacological models; effects also shown in small clinical studies. Scavenging of reactive oxygen species released from inflammatory cells is a likely contributor to these anti-inflammatory effects. Ciclopirox, and its olamine salt, is available in multiple topical formulations, suitable for administration onto the skin and nails and into the vagina. The pharmaceutical forms most widely investigated are 1% ciclopirox olamine cream and 8% ciclopirox acid nail lacquer, but lotion, spray, shampoo, pessary, solution, gel and douche formulations have also been used. Ciclopirox penetrates into the deep layers of the skin, mucosal membranes and nail keratin, reaching concentrations exceeding the minimal fungicidal concentrations for most medically important fungi. A large number of clinical trials were and are still being performed with ciclopirox, starting in the early 1980s. Ciclopirox was first developed for fungal skin infections and vaginal candidiasis, and is currently well established in these indications. More recently, the drug has been clinically investigated in seborrhoeic dermatitis and onychomycosis, showing good efficacy and excellent tolerability. Emphasis in this review is given to a ciclopirox medicated nail lacquer, which is based on an original technology and has superior properties in terms of its affinity to keratin and nail permeation. It has been found to have superior efficacy and safety to another commercially available formulation in the treatment of onychomycosis. The safety features of ciclopirox are well known. The topical drug is devoid of systemic adverse reactions. Mild local reactions characterized by a burning sensation of the skin, irritation, redness, pain or pruritus, generally in less than 5% of treated patients, can be observed following skin and vaginal application. With nail application, the most common adverse event is the appearance of mild erythema in 5% of the treated population. As a general conclusion...

Potential of Ergosterol Synthesis Inhibitors To Cause Resistance or Cross-Resistance in Trichophyton rubrum

“…Unlike those antifungal agents, CPX does not affect sterol biosynthesis and is not metabolized via cytochrome P450 (12). Interestingly, in the present study, no mutant resistant to CPX was obtained, thus suggesting that, under our experimental conditions, T. rubrum has no biochemical or molecular capacity to develop resistance to this drug, even after prolonged exposure to subinhibitory drug concentrations for several growth generations.…”

“…Ciclopirox (CPX) is a hydroxypyridone which exhibits activity against nearly all the clinically relevant dermatophytes, yeasts, and molds. The main mechanism of action of CPX is its high affinity for trivalent cations (such as Fe 3ϩ ), resulting in the inhibition of many metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell (12). CPX and its olamine salt are available in multiple topical formulations, suitable for administration to the skin, nails, and vaginal mucosa (12).…”

Evaluation of the Efficacy of ME1111 in the Topical Treatment of Dermatophytosis in a Guinea Pig Model

“…The improved efficacy of ME1111 over that of 8% ciclopirox is most likely due to its physiochemical properties, such as its low molecular weight and low affinity to keratin (3). Ciclopirox is a topical antimycotic agent belonging to the chemical class of hydroxypyridones and is not related to azoles (8). Unlike currently available agents, ME1111 targets the succinate dehydrogenase (complex II) of dermatophyte species.…”

Development of a Kinetic Spectrophotometry Method for the Determination of Ciclopirox Olamine in Pharmaceutical Sample

“…Ciclopirox olamine (CXO), 6-cyclohexyl-1-hydroxy-4methyl-2(1H)-pyridona is a synthetic hydroxypyridone, with fungicide action of broadspectrum that inhibits the growth of pathogenic dermatophytes (skin fungi, hair and nail) 1,2,3 . This drug has a half-life of 1.7 h and renal excretion.…”

“…Studies with human skin of corpses showed capillar penetration through the epidermis to the hair follicles and sebaceous glands, while a portion of the drug remains in the stratum corneum 4 and it presents systemic absorption when applied in cream 1% (CXO). The mechanism of action is related to its chelating action on polyvalent metal cations such as Fe (III) and Al (III) essential for two fungus enzymes, catalase and peroxidase 2,5 . The USP has published two standard methods for the determination of CXO in pharmaceutical formulations, by HPLC 6 and spectrophotometry 7 .…”