Ciclopirox (sometimes known by the abbreviation CPX) is a synthetic

antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as ...

agent for topical dermatologic treatment of superficial mycoses. It is most useful against

tinea versicolor Tinea versicolor (also pityriasis versicolor) is a condition characterized by a skin eruption on the trunk and proximal extremities. The majority of tinea versicolor is caused by the fungus '' Malassezia globosa'', although '' Malassezia furfur'' ...

. It is sold under many brand names worldwide.Drugs.co
International brand names for ciclopirox
Page accessed January 201, 2016

Medical uses

Ciclopirox is indicated for the treatment of

tinea pedis Dermatophytosis, also known as ringworm, is a fungal infection of the skin. Typically it results in a red, itchy, scaly, circular rash. Hair loss may occur in the area affected. Symptoms begin four to fourteen days after exposure. Multiple ...

and

tinea corporis Tinea corporis is a fungal infection of the body, similar to other forms of tinea. Specifically, it is a type of dermatophytosis (or ringworm) that appears on the arms and legs, especially on glabrous skin; however, it may occur on any superficial ...

due to ''

Trichophyton rubrum ''Trichophyton rubrum'' is a dermatophytic fungus in the phylum Ascomycota. It is an exclusively clonal, anthropophilic saprotroph that colonizes the upper layers of dead skin, and is the most common cause of athlete's foot, fungal infectio ...

'', ''

Trichophyton mentagrophytes ''Trichophyton mentagrophytes'' is a species in the fungal genus '' Trichophyton''. It is one of three common fungi which cause ringworm in companion animals. It is also the second-most commonly isolated fungus causing tinea infections in huma ...

'' and '' Epidermophyton floccosum'', as well as

seborrheic dermatitis Seborrhoeic dermatitis, sometimes inaccurately referred to as seborrhoea, is a long-term skin disorder. Symptoms include red, scaly, greasy, itchy, and inflamed skin. Areas of the skin rich in oil-producing glands are often affected including the ...

. It is not to be used in the eyes or vagina, and nursing women should consult their doctors before use, since it is not known whether ciclopirox passes into

human milk Breast milk (sometimes spelled as breastmilk) or mother's milk is milk produced by mammary glands located in the breast of a human female. Breast milk is the primary source of nutrition for newborns, containing fat, protein, carbohydrates (lacto ...

. A burning sensation may be felt when first applying ciclopirox on the skin.

Nail infections

In addition to other formulations, ciclopirox is used in

lacquers Lacquer is a type of hard and usually shiny coating or finish applied to materials such as wood or metal. It is most often made from resin extracted from trees and waxes and has been in use since antiquity. Asian lacquerware, which may be ca ...

for topical treatment of onychomycosis (fungal infections of the nails). A

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting m ...

of the six trials of nail infections available in 2009 concluded that they provided evidence that topical ciclopirox had poor cure rates, and that

amorolfine Amorolfine (or amorolfin), is a morpholine antifungal drug that inhibits Δ14-sterol reductase and cholestenol Δ-isomerase, which depletes ergosterol and causes ignosterol to accumulate in the fungal cytoplasmic cell membranes. Marketed as Cur ...

might be substantially more effective, but more research was required. "Combining data from 2 trials of ciclopiroxolamine versus placebo found treatments failure rates of 61% and 64% for ciclopiroxolamine. These outcomes followed long treatment times (48 weeks) and this makes ciclopiroxolamine a poor choice for nail infections. Better results were observed with the use of amorolfine lacquer; 6% treatment failure rates were found after 1 month of treatment but these data were collected on a very small sample of people and these high rates of success might be unreliable." Efinaconazole, an

azole antifungal An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryp ...

, led to cure rates two or three times better than the next-best topical treatment, ciclopirox.

Pharmacology

Pharmacodynamics

In contrast to the

azole Azoles are a class of five-membered heterocyclic compounds containing a nitrogen atom and at least one other non-carbon atom (i.e. nitrogen, sulfur, or oxygen) as part of the ring. Their names originate from the Hantzsch–Widman nomenclature. T ...

s and other antimycotic drugs, the

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...

of ciclopirox is poorly understood. However, loss of function of certain

catalase Catalase is a common enzyme found in nearly all living organisms exposed to oxygen (such as bacteria, plants, and animals) which catalyzes the decomposition of hydrogen peroxide to water and oxygen. It is a very important enzyme in protecting t ...

and

peroxidase Peroxidases or peroxide reductases ( EC numberbr>1.11.1.x are a large group of enzymes which play a role in various biological processes. They are named after the fact that they commonly break up peroxides. Functionality Peroxidases typically ca ...

enzymes has been implicated as the mechanism of action, as well as various other components of cellular metabolism. In a study conducted to further elucidate ciclopirox's mechanism, several ''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have b ...

'' mutants were screened and tested. Results from interpretation of the effects of both the drug treatment and mutation suggested that ciclopirox may exert its effect by disrupting DNA repair, cell division signals and structures (mitotic spindles) as well as some elements of intracellular transport. It is currently being investigated as an alternative treatment to

ketoconazole Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous ca ...

for seborrhoeic dermatitis as it suppresses growth of the yeast ''Malassezia furfur''. Initial results show similar efficacy to ketoconazole with a relative increase in subjective symptom relief due to its inherent anti-inflammatory properties.

Chemistry

Ciclopirox is a N-hydroxypyridone. Structurally, ciclopirox is the ''N''-oxide of a 2-hydroxypyridine derivative and therefore can be termed a hydroxypyridine antifungal agent. Additionally, the structure as drawn above is the lactam

tautomer Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hy ...

and indicates the molecule being an N-hydroxy-2-pyridone. Hence the classification of ciclopirox as a 2-pyridone antifungal agent. Ciclopirox is used clinically as ''ciclopirox olamine'', the olamine

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quant ...

of ciclopirox.

References

{{Gynecological anti-infectives and antiseptics 2-Pyridones Antifungals Cyclohexyl compounds