Penlac (Ciclopirox)
Ciclopirox
Brand Name(s): Loprox®, Loprox TS®, Penlac™
Classification:
» Antiinfective Agents
» Antifungals
Dermatological Agents
» Topical Antiinfectives
» Antifungals
Description: Ciclopirox olamine is a topical antifungal agent which has antifungal activity similar to the imidazoles. The 1% cream and lotion formulations are well-tolerated and have similar efficacy compared to clotrimazole. They are used primarily for the treatment of tinea pedis, tinea cruris, tinea corporis (ring worm), and tinea versicolor. Loprox® 1% cream was approved by the FDA in 1982, and subsequently the 1% lotion was introduced in 1988; the concentrations of these formulations were later reduced to 0.77%. The lotion was discontinued in January 2003. The new formulation, Loprox® TS, is a hybrid of the cream and lotion formulations to give a thicker texture; it is considered therapeutically equivalent to the lotion. Penlac™ Nail Lacquer (Ciclopirox) Topical Solution (8%) was approved by the FDA on December 17th, 1999 for the topical treatment of mild to moderate onychomycosis of the fingernails or toenails without lunula involvement in immunocompetent patients. A 1% shampoo was approved February 28, 2003 for treatment of seborrheic dermatitis of the scalp.
Mechanism of Action: Ciclopirox is a substituted pyridone antimycotic with activity against a broad spectrum of dermatophytes, yeasts, actinomycetes, molds, other fungi and some gram-positive and gram-negative bacteria. Although the exact cellular mechanisms are unknown, ciclopirox is thought to exert its antifungal and antibacterial activity by blocking fungal transmembrane transport, causing intracellular depletion of essential substrates (e.g., amino acids) and/or ions (e.g., potassium). Ciclopirox interferes with the synthesis of RNA and DNA. At high ciclopirox concentrations, the fungal cell membrane permeability is altered, allowing leakage of intracellular material. Ciclopirox does not inhibit synthesis nor cause lysis of the fungal cell wall. One in vitro study suggested that ciclopirox acts by chelation of polyvalent cations (Fe+3 or Al+3) resulting in inhibition of the metal-dependent enzymes that are responsible for the degradation of peroxides within the fungal cell; the clinical significance of this observation is not known.
Ciclopirox has fungicidal activity against in vitro isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporum canis, and Candida albicans. Ciclopirox also inhibits the growth of pathogenic dermatophytes, yeasts, and Malassezia furfur. Although not used for its antibacterial properties, ciclopirox has some activity against Trichomonas vaginalis and Mycoplasma.
In vitro susceptibility testing methods for determining ciclopirox MIC values against the dermatophytic molds, including Trichophyton rubrum species, have not been standardized or validated. Breakpoints to determine whether clinical isolates of Trichophyton rubrum are susceptible or resistant to ciclopirox have not been established. Due to variation in laboratory techniquies, Trichophyton rubrum and Trichophyton mentagrophytes species are associated with a broad range of ciclopirox MIC values (range 1-20 ug/mL).
Ciclopirox Topical Suspension (Lotion 0.77 %) 
Studies have not been conducted to evaluate drug resistance development in Trichophyton rubrum species exposed to ciclopirox. Studies assessing cross-resistance to ciclopirox and other known antifungal agents have not been performed.
The relevance of the antifungal properties of ciclopirox for the indication of seborrheic dermatitis is not known.
Pharmacokinetics: Ciclopirox olamine is administered topically and is distributed to the stratum corneum, epidermis, hair follicles, sebaceous glands, and dermis. Topical ciclopirox also penetrates into fingernails and toenails. Studies investigating ciclopirox disposition after oral administration demonstrate that ciclopirox is primarily renally excreted as glucuronides (about 94%) or as unchanged drug. Fecal excretion is negligible.
Ciclopirox, when applied as a topical 1% solution is approximately 1.3% systemically absorbed when applied to 750 cm2 of back skin which is occluded for 6 hours. The drug half-live is 1.7 hours. Two days after application, only 0.01% of the dose is recovered in the urine. Penetration studies for Loprox® 1% lotion in human cadaverous skin resulted in 0.8 to 1.6% of the dose in the stratum corneum 1.5 to 6 hours after application. Penetration studies demonstrate that the 1% cream has equivalent systemic absorption to the 1% lotion.
Systemic absorption of ciclopirox nail solution was determined in five patients with dermatophytic onychomycoses, after once daily application to all 20 digits and adjacent 5 mm of skin for six months. In this study, ciclopirox serum levels ranged from 12-80 ng/mL. Based on urinary data, the mean absorption of ciclopirox was <5% of the applied dose. One month after discontinuing treatment, the serum and urine ciclopirox concentrations were below the detection limit. The in vitro penetration of the ciclopirox nail solution was evaluated by application of radiolabeled ciclopirox to onychomycotic toenails that were avulsed; the drug penetrated to a nail depth of approximately 0.4 mm. As expected, nail plate concentrations decreased with nail depth. The clinical significance of these findings is unknown.
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[ Revised 6/23/2006 12:52:00 PM ]
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