Penlac
The dermatopharmacologic profile of ciclopirox 8% nail lacquer.

Bohn M, Kraemer K.

Dermatologic Division, Aventis Pharma Deutschland GmbH, Frankfurt am Main, Germany.

Ciclopirox 8% nail lacquer is a recently introduced topical formulation of the hydroxypyridone antimycotic ciclopirox. In vitro data indicate that ciclopirox has activity against the important pathogenic dermatophytes responsible for onychomycosis. The lacquer delivery system provides a high concentration gradient for the transfer of the antifungal agent through the nail plate. Daily application to the toenail surface of healthy subjects resulted in good penetration and distribution within all nail layers. Systemic absorption of ciclopirox in five patients with onychomycosis was minimal.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11107709&dopt=Abstract ciclopirox Penlac



Penlac
[Treatment of therapy refractory verrucae vulgares with a ciclopirox-containing lacquer]

[Article in German]

Szeimies RM, Wimmershoff MB, Reisberger EM, Landthaler M.

Klinik und Poliklinik fur Dermatologie, Klinikum der Universitat Regensburg, 93042 Regensburg. Rolf-Markus.Szeimies klinik.uni-regensburg.de

BACKGROUND AND OBJECTIVE: Anti-inflammatory actions of ciclopirox, an antifungal agent, have been described previously. We assessed the effectiveness of ciclopirox in the treatment of viral warts. PATIENTS/METHODS: Twenty-three immunocompetent patients (age 9-61 years) with common warts at the hands, feet and in the face resistant to conventional therapy were treated. Following keratolysis with a salicylic acid-containing patch, an 8% ciclopirox lacquer was applied 1-2 times daily. At the beginning and the end of the treatment lesions were photographed and the time span (minimum 4 weeks) until complete resolution was documented. RESULTS: In 7 patients complete remission, and in 12 patients partial remission was achieved. Only 4 patients did not show any effect under topical ciclopirox treatment (mean duration of therapy 3.2 +/- 2.1 months). The overall response rate was 82.6%. Local side effects like erythema or pruritus were not reported. CONCLUSION: Our data suggest that a ciclopirox lacquer may be helpful in the treatment of common warts. However, the data have to be confirmed in a randomized controlled trial in the future.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11428076&dopt=Abstract ciclopirox Penlac



Penlac
[Mode of action of ciclopiroxolamine on Candida albicans]

[Article in German]

Niewerth M, Schaller M, Korting HC, Hube B.

Robert Koch-Institut, Nordufer 20, D-13353 Berlin, Germany. niewerthm rki.de

Candida albicans is a common pathogen causing both superficial and invasive mycoses. The hydroxypyridone ciclopiroxolamine belongs to antimycotic drugs used for treatment of superficial mycoses. Whereas the mode of action of other antimycotics, for example the azoles, is well known, the specific action of ciclopiroxolamine is poorly understood. There are hints, that ciclopiroxolamine acts as a potential chelating agent and influences some cellular processes by chelating metal ions. Consequently, the antimycotic effectiveness of ciclopiroxolamine could be due to a general reduced viability of the fungus, or due to a higher sensitivity of a fungus against the human immune system as well as due to a reduced capability to produce some specific virulence factors that are indispensable for infection. Nevertheless, iron metabolism seems to play a major role in its effect.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12073566&dopt=Abstract ciclopirox Penlac



Penlac
The antifungal drug ciclopirox inhibits deoxyhypusine and proline hydroxylation, endothelial cell growth and angiogenesis in vitro.

Clement PM, Hanauske-Abel HM, Wolff EC, Kleinman HK, Park MH.

Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA.

The hypusine biosynthetic steps represent novel targets for intervention in cell proliferation. Hypusine is a rare amino acid, formed posttranslationally in one cellular protein, eIF5A, and is essential for cell proliferation. Deoxyhypusine hydroxylase, the metalloenzyme catalyzing the final step in hypusine biosynthesis, and prolyl 4-hydroxylase, a non-heme iron enzyme critical for collagen processing, can be inhibited by small chelating molecules that target their essential metal atom. We examined the effects of 5 compounds (ciclopirox, deferiprone, deferoxamine, mimosine and 2,2'-dipyridyl) on these protein hydroxylases in HUVECs, on cell proliferation and on angiogenesis using 2 model assays: tube-like vessel formation on Matrigel and the chick aortic arch sprouting assay. These compounds inhibited cellular deoxyhypusine hydroxylase in a concentration-dependent manner, but their efficacy varied widely in the following order: ciclopirox--> deferoxamine-->2,2'-dipyridyl-->deferiprone-->mimosine (IC(50) 5-200 microM). Inhibition of DNA synthesis, following the same order (IC(50) 10-450 microM), correlated with G(1) arrest of the cell cycle. These compounds also inhibited proline hydroxylation and maturation of collagen in HUVECs and caused inhibition of angiogenesis in vitro. Of the compounds tested, ciclopirox was by far the most effective inhibitor of HUVEC proliferation and angiogenesis. The strong antiangiogenic activity of this readily available antifungal drug along with its antiproliferative effects suggests a new potential application for ciclopirox in the treatment of solid tumors.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12115536&dopt=Abstract ciclopirox Penlac



Penlac
Ciclopirox prevents peroxynitrite toxicity in astrocytes by maintaining their mitochondrial function: a novel mechanism for cytoprotection by ciclopirox.

Choi JJ, Kong MY, Lee SJ, Kim HC, Ko KH, Kim WK.

Department of Pharmacology, College of Medicine, Ewha Institute of Neuroscience, Ewha Women's University, 70 Chongro-6-ga, Chongro-ku, Seoul 110-783, South Korea.

Previously we have reported that astrocytes deprived of glucose were highly vulnerable to peroxynitrite (Choi and Kim, J. Neurosci. Res. 54 (1998) 870; Neurosci. Lett. 256 (1988) 109; Ju et al., J. Neurochem. 74 (2000) 1989). Here we report that ciclopirox, which is clinically used as an anti-fungal agent, completely prevents the increased death in glucose-deprived astrocytes exposed to 3-morpholinosydnonimine (SIN-1, a peroxynitrite-releasing reagent). The increased vulnerability was in good correlation with the peroxynitrite-evoked decrease of mitochondrial transmembrane potential (MTP) in astrocytes. A simultaneous exposure to glucose deprivation and SIN-1 rapidly depolarized MTP and depleted ATP in astrocytes. Inclusion of ciclopirox initially increased the MTP, maintained it high, and blocked the ATP depletion in glucose-deprived SIN-1-treated astrocytes. However, ciclopirox did not prevent the depletion of reduced glutathione in glucose-deprived SIN-1-treated astrocytes. Consistently, ciclopirox did not scavenge various kinds of oxidants including peroxynitrite, nitric oxide, superoxide anion, hydrogen peroxide and hydroxyl radical. Ciclopirox has been experimentally used as a cell cycle G1/S phase transition blocker (Hoffman et al., Cytometry 12 (1991) 26). Flow cytometry analysis, however, showed that the cytoprotective effect of ciclopirox was not attributed to its inhibition of the cell cycle progression. The present results indicate that ciclopirox protects astrocytes from peroxynitrite cytotoxicity by attenuating peroxynitrite-induced mitochondrial dysfunction.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12243770&dopt=Abstract ciclopirox Penlac