Penlac
[Ciclopiroxolamine in the topical treatment of vaginal mycoses]

[Article in Italian]

Bucciero A, Molteni E, Molteni B, Mariani W, Jacobellis M.

We have verified the local activity and tolerance of the antimycotic drug ciclopiroxolamine in an open trial. The study included 34 women suffering from clinically and mycologically diagnosed vulvovaginitis caused by Candida. The therapy consisted of inserting a 100 mg ovule of ciclopiroxolamine once a day for 3 days. The cultural examination was negative in 76.5% of cases at the 1st control after the treatment and in 82.3% of cases at the 2nd control after the treatment. All the considered subjective and objective symptoms showed a highly significant decrease of frequency and intensity. No chemical parameter was modified; only in one patient a very mild side effect was verified.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2771141&dopt=Abstract ciclopirox Penlac



Penlac
[In vitro antifungal spectrum of ciclopiroxolamine]

[Article in French]

Goudard M, Regli P, Lubrano N.

Laboratoire de Botanique et Cryptogamie, Faculte de Pharmacie, Marseille.

The ciclopiroxolamine is a new synthetic antifungal agent related to pyridones; it is the ethanolamine salt of the pyridone acid 6-cyclohexyl 1-hydroxy 4-methyl 2 (1H). The antifungal properties of this molecule was tested in vitro against pathogenic species such as yeasts. (Candida, Torulopsis, Malassezia), moulds (Aspergillus, Scopulariopsis) and dermatophytes, (Microsporum, Trichophyton, Epidermophyton) using an agar dilution method (Sabouraud or Dixon). The results seem to be remarkably homogeneous whatever the strain tested. The MIC obtained with moulds (less sensitive) range between 10-20 micrograms/ml. Whereas they range between 1 and 10 micrograms/ml with yeasts and dermatophytes. On account of the lack of in vivo toxicity of ciclopiroxolamine and of the level of concentrations used in dermatology (1% ointment), the ciclopiroxolamine has a particularly interesting broad spectrum on fungi which induce cutaneous mycoses.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2797886&dopt=Abstract ciclopirox Penlac



Penlac
Evaluation of fungicidal action in vitro and in a skin model considering the influence of penetration kinetics of various standard antimycotics.

Hanel H, Raether W, Dittmar W.

Hoecsht AG, Frankfurt, Federal Republic of Germany.

Ciclopiroxolamine (Loprox) was the first representative of hydroxpyridones to be developed as a topical antifungal. In the microtitration test and in a skin model using excised skin prices of slaughtered pigs, the fungistatic and fungicidal activity as well as the penetration kinetics of ciclopiroxolamine and ciclopirox were compared with those of the azole compounds bifonazole, clotrimazole, econazole, miconazole, oxiconazole, and tioconazole, and with other antimycotics such as naftifine, sulbentine, tolciclate, and tolnaftate. Clotrimazole had an in vitro inhibitory activity superior to that of the hydroxypyridone ciclopiroxolamine; the latter compound, however, exhibited faster penetration and higher inhibitory or fungicidal activity than the azoles and other antimycotics in the pig skin model. Studies of cream formulations with antimycotics at the bottom layer of the stratum corneum (close to the stratum granulosum) showed that ciclopiroxolamine cream had the most prominent inhibitory effect (93%) and the highest fungicidal activity (98%). The other antimycotics tested exhibited growth inhibition rates of 50% or less and lower fungicidal rates. Inoculated pig skin was treated with lacquer formulations to show that ciclopirox completely inhibited the growth of Trichophyton mentagrophytes, whereas the clotrimazole-treated samples allowed only 0.47% growth. The fungicidal activity of lacquer formulations was 99% for ciclopirox and around 90% for most of the azoles on the pig skin model. The necessity of models tackling the complex penetration kinetics in human skin was discussed.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3214073&dopt=Abstract ciclopirox Penlac



Penlac
Dermatopharmacology of ciclopirox nail lacquer topical solution 8% in the treatment of onychomycosis.

Bohn M, Kraemer KT.

Aventis Pharmaceuticals, Inc, Frankfurt.

Ciclopirox is a synthetic hydroxypyridone antifungal agent. In contrast to the azoles, glucuronidation is the main metabolic pathway of ciclopirox; therefore interactions with drugs metabolized via the cytochrome P(450) system are unlikely. Ciclopirox is also distinct from the common systemic agents, which interfere with sterol biosynthesis. In fact, ciclopirox chelates trivalent cations (such as Fe(3+)), inhibits metal-dependent enzymes that are responsible for degradation of toxic metabolites in the fungal cells, and targets diverse metabolic (eg, respiratory) and energy producing processes in microbial cells. Ciclopirox is a broad spectrum antimicrobial with activity against all the usual dermatophytes as well as yeast and nondermatophyte molds. It has demonstrated activity against gram positive and negative bacteria, including resistant strains of Staphylococcus aureus. Ciclopirox exhibits fungal inhibitory activity (minimum inhibitory concentration < 4 microg/mL for dermatophytes) as well as fungicidal activity; to date resistance to the drug has not been identified. Ciclopirox has been formulated in a nail lacquer delivery system. After evaporation of volatile solvents in the lacquer, the concentration of ciclopirox in the remaining lacquer film reaches approximately 35%, providing a high concentration gradient for penetration into the nail. Radiolabel data demonstrate penetration into infected nails after only 1 application of the lacquer. Ciclopirox nail lacquer is a topical product that provides an active fungicidal agent in a delivery system capable of promoting nail penetration. With repeated applications, the antifungal agent is homogeneously distributed through all layers of the toenail achieving concentrations of ciclopirox in excess of inhibitory and fungicidal concentrations for most pathogens. Although ciclopirox readily penetrates nails, very low levels of ciclopirox are recoverable systemically, even after chronic use. Ciclopirox nail lacquer 8% is a topical product that provides an active fungicidal agent in a delivery system capable of penetrating nails.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11002197&dopt=Abstract ciclopirox Penlac



Penlac
Ciclopirox nail lacquer topical solution 8% in the treatment of toenail onychomycosis.

Gupta AK, Fleckman P, Baran R.

Division of Dermatology, Department of Medicine, Sunnybrook and Women's College Health Sciences Center (Sunnybrook site), and the University of Toronto, the Division of Dermatology, Department of Medicine, University of Washington, Seattle, and the Nail Research Center, Cannes.

BACKGROUND: Onychomycosis is a relatively common condition affecting toenails more than fingernails. It is caused predominantly by dermatophytes. Onychomycosis can cause pain and discomfort and has the potential to be a source of morbidity. OBJECTIVE: We evaluated the efficacy and safety of ciclopirox nail lacquer solution 8% used to treat onychomycosis of the toe in the United States and in centers worldwide. METHODS: Two identically designed, double-blind, vehicle controlled, parallel group multicenter studies were performed in the United States to evaluate the use of ciclopirox nail lacquer to treat mild to moderate toe onychomycosis caused by dermatophytes. In the first study, 223 patients were randomized to treatment (ciclopirox group: 112, vehicle group: 111), and in the second study, 237 subjects were randomized (ciclopirox group: 119, vehicle group: 118). Before randomization, patients were to have clinical features of onychomycosis in at least one great toe with positive light microscopic examination and a positive dermatophyte culture. The test material was applied daily for a period of 48 weeks to all toenails and affected fingernails, covering the entire nail plate and approximately 5 mm of surrounding skin. At baseline, subjects had between 20% to 65% area of target nail involved. Physician's assessments were carried out every 4 weeks, and mycologic evaluation and photographic planimetry using standardized photographs were performed every 12 weeks during the 48 weeks of treatment. In studies conducted outside the United States, patients were also to have clinical, microscopic, and culture evidence of onychomycosis. However, these studies included some patients infected with nondermatophyte organisms (eg, Candida species), and the area of nail involvement was generally greater than observed in the US studies. Treatment regimens also varied in the non-US studies with lacquer applications that were sometimes less frequent than the once daily treatment used in the US studies (eg, alternate day or twice weekly). In addition, the typical duration of treatment was 6 months in the non-US studies as compared with 48 weeks in the United States. Outcome measures were similar to those used in the US trials, although a non-photographic planimetric method was used to quantify disease extent. RESULTS: Data from the pivotal US trials have demonstrated that ciclopirox nail lacquer 8% topical solution is significantly more effective than placebo in the treatment of onychomycosis caused by Trichophyton rubrum, and of mild to moderate toe onychomycosis without lunula involvement. At the end of the 48-week treatment period, the mycologic cure rate (negative culture and negative light microscopy) in study I was 29% vs 11% in the ciclopirox and vehicle groups, respectively. Similarly, the mycologic cure rate for study II was 36% vs 9%, respectively. In the non-US studies, the mycologic cure rates ranged from 46.7% to 85.7%. In addition, ciclopirox nail lacquer has demonstrated a broad spectrum of activity with efficacy against Candida species and some nondermatophytes in non-US studies. Ciclopirox nail lacquer is considered extremely safe regarding causally related treatment emergent adverse-effects (TEAEs), with most TEAEs transient and localized to the site of action (eg, erythema and application site reaction). In the US studies, TEAEs were generally mild and cleared while the patient continued to use the nail lacquer. CONCLUSIONS: Studies conducted worldwide demonstrate the efficacy of ciclopirox nail lacquer for the treatment of finger and toe onychomycosis. Both controlled and open-label studies confirm the excellent safety profile of this topical therapy. Thus, the nail lacquer provides a treatment choice with a favorable benefit-to-risk ratio. With its novel mechanism of action and its topical route of administration, ciclopirox nail lacquer offers an innovative approach to the treatment of this often difficult-to-manage disease.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11002198&dopt=Abstract ciclopirox Penlac