Ciclopirox

Ciclopirox is a synthetic antifungal agent for topical dermatologic treatment of superficial mycoses. It is most useful against Tinea versicolor. It is sold under many brand names worldwide.[1]

Ciclopirox

Clinical data
Trade names	Many brand names worldwide[1]
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a604021
Pregnancy category	B
Routes of administration	Topical (applied as a nail lacquer, skin cream or shampoo)
ATC code	D01AE14 (WHO) G01AX12 (WHO)
Legal status
Legal status	US: ℞-only Rx-only (CA)
Pharmacokinetic data
Bioavailability	<5% with prolonged use
Protein binding	94 to 97%
Elimination half-life	1.7 hours
Identifiers
IUPAC name 6-cyclohexyl-1-hydroxy-4-methylpyridin-2(1H)-one
CAS Number	29342-05-0
PubChem CID	2749
DrugBank	DB01188
ChemSpider	2647
UNII	19W019ZDRJ
KEGG	D03488
ChEBI	CHEBI:453011
ChEMBL	ChEMBL1413
CompTox Dashboard (EPA)	DTXSID9048564
ECHA InfoCard	100.045.056
Chemical and physical data
Formula	C12H17NO2
Molar mass	207.269 g·mol^−1
3D model (JSmol)	Interactive image
SMILES O=C1/C=C(\C=C(/N1O)C2CCCCC2)C
InChI InChI=1S/C12H17NO2/c1-9-7-11(13(15)12(14)8-9)10-5-3-2-4-6-10/h7-8,10,15H,2-6H2,1H3 Key:SCKYRAXSEDYPSA-UHFFFAOYSA-N
(verify)

Medical uses

Ciclopirox is indicated for the treatment of tinea pedis and tinea corporis due to Trichophyton rubrum, Trichophyton mentagrophytes and Epidermophyton floccosum, as well as seborrheic dermatitis. 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. A burning sensation may be felt when first applying ciclopirox on the skin.[2]

Nail infections

In addition to other formulations, ciclopirox is used in lacquers for topical treatment of onychomycosis (fungal infections of the nails). A meta-analysis 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 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."[3]

Pharmacology

Pharmacodynamics

In contrast to the azoles and other antimycotic drugs, the mechanism of action of ciclopirox is poorly understood.[4] However, loss of function of certain catalase and peroxidase 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 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.[5]

It is currently being investigated as an alternative treatment to ketoconazole 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.[6]

Chemistry

Ciclopirox is a considered a hydroxypyrimidine (sic) antifungal agent. Structurally, ciclopirox is the N-oxide of a 2-hydroxypyridine derivative and therefore ought to be termed a hydroxypyridine antifungal agent. Additionally, the structure as drawn above is the lactam tautomer 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 of ciclopirox.

References

1. Drugs.com International brand names for ciclopirox Page accessed January 201, 2016
2. "Ciclopirox Olamine Antifungal Shampoo". Okdermo. Retrieved 2019-08-06.
3. Crawford F (1996). "Topical treatments for fungal infections of the skin and nails of the foot". Reviews. 319 (7202): 79–82. doi:10.1002/14651858.CD001434.pub2. PMC 28154. PMID 10398626.
4. Niewerth M, Kunze D, Seibold M, Schaller M, Korting HC, Hube B (June 2003). "Ciclopirox Olamine Treatment Affects the Expression Pattern of Candida albicans Genes Encoding Virulence Factors, Iron Metabolism Proteins, and Drug Resistance Factors". Antimicrobial Agents and Chemotherapy. 47 (6): 1805–1817. doi:10.1128/AAC.47.6.1805-1817.2003. PMC 155814. PMID 12760852.
5. Leem SH, Park JE, Kim IS, Chae JY, Sugino A, Sunwoo Y (2003). "The possible mechanism of action of ciclopirox olamine in the yeast Saccharomyces cerevisiae". Mol. Cells. 15 (1): 55–61. PMID 12661761.
6. Ratnavel RC, Squire RA, Boorman GC (2007). "Clinical efficacies of shampoos containing ciclopirox olamine (1.5%) and ketoconazole (2.0%) in the treatment of seborrhoeic dermatitis". J Dermatolog Treat. 18 (2): 88–96. doi:10.1080/16537150601092944. PMID 17520465. S2CID 34852507.