RESUMEN
BACKGROUND: A new water-soluble formulation with ciclopirox has shown a higher penetration than other ciclopirox nail lacquers currently marketed, thus providing a higher concentration of ciclopirox into the nail. OBJECTIVE: To evaluate the efficacy and safety of a new ciclopirox nail hydrolacquer compared with its vehicle and an active comparator (hydroxypropyl chitosan-based 80 mg/g ciclopirox nail lacquer) for the treatment of toenail fungal infection. METHODS: Phase III, multicenter, randomised, double-blind, clinical trial in patients with distal mild to moderate toenail onychomycosis due to dermatophyte fungi. Patients were randomised to apply topically a ciclopirox nail hydrolacquer, its vehicle or a reference product once daily for 48 weeks with a follow-up period of 4 weeks up to week 52. RESULTS: A total of 381 patients were included. No statistically significant differences were observed between patient groups in the proportion of subjects achieving a complete cure. At week 52, a higher percentage of patients in the ciclopirox nail hydrolacquer group achieved a mycological cure (negative for culture and DTS/KOH test, with results: 32.0% ciclopirox nail hydrolacquer, 23.2% vehicle and 27% reference product, respectively), and similar results were found for improvement (mycological cure and reduction of diseased nail ≥20%, with results: 27.2% ciclopirox nail hydrolacquer, 21.6% vehicle and 20.6% reference product, respectively). Regarding mycological results, only ciclopirox nail hydrolacquer demonstrated significant statistical superiority versus vehicle negativizing dermatophyte culture (p = .039) with no recurrences, relapses or re-infections in a four-week follow-up patients with complete cure. The safety profile was comparable to the vehicle and reference product and consistent with the previously reported. CONCLUSIONS: A new water-soluble formulation for a ciclopirox nail lacquer showed similar efficacy to the reference product to eradicate toenail onychomycosis and superiority in the mycological cure defined by negative culture, thus preventing reinfections and recurrences. Efficacy and safety data demonstrate the positive benefit-risk profile of this new topical antifungal preparation. [Correction added on 13 April 2023, after first online publication: The results and conclusions in the Abstract contained incorrect information and were revised in this version.].
Asunto(s)
Dermatosis del Pie , Onicomicosis , Humanos , Adulto , Onicomicosis/tratamiento farmacológico , Onicomicosis/microbiología , Ciclopirox/efectos adversos , Uñas , Piridonas/efectos adversos , Administración Tópica , Antifúngicos/efectos adversos , Dermatosis del Pie/tratamiento farmacológico , Agua , Resultado del TratamientoRESUMEN
The maturation and secretion of interleukin-1ß (IL-1ß) mediated by NLRP3 inflammasome activation plays an important role in the progression of many inflammatory diseases. Inhibition of NLRP3 inflammasome activation may be a promising strategy to treat these inflammation-driven diseases, such as psoriasis. As a broad-spectrum antifungal agent, ciclopirox (CPX) is widely used in the treatment of dermatomycosis. Although CPX has been reported to have anti-inflammatory effects in many studies, there has been little research into its underlying mechanisms. In our study, CPX reduced lipopolysaccharide (LPS)/nigericin-induced NLRP3 inflammasome activation (IC50: 1.684 µM). Mechanistically, CPX upregulated peroxisome proliferator-activated receptor-γ coactivator-1α expression (by 82.7% at 5 µM and 87.5% at 10 µM) to protect mitochondria. Our studies showed that CPX reduced mitochondrial reactive oxygen species production, increased mitochondrial membrane potential, elevated mitochondrial biosynthesis, and up-regulated intracellular adenosine triphosphate level. Furthermore, treatment with CPX promoted the up-regulation of mRNA expression, which involved mitochondrial biosynthesis (NRF1, NRF2, TFAM) and antioxidation (SOD1 and CAT). In addition, CPX ameliorated inflammatory response in imiquimod-induced psoriasis mice. This study provides a potential pharmacological mechanism for CPX to treat psoriasis and other NLRP3-driven inflammatory diseases.
Asunto(s)
Proteína con Dominio Pirina 3 de la Familia NLR , Psoriasis , Animales , Ciclopirox/efectos adversos , Imiquimod/efectos adversos , Inflamasomas/metabolismo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , Mitocondrias , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Psoriasis/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
BACKGROUND: Ciclopirox (CPX), a broad-spectrum fungicide, has been widely used to treat fungal infection on the skin and nails for decades. Recent preclinical and clinical studies have shown that CPX also possesses promising anticancer activity. OBJECTIVE: The objective of this study is to summarize the patents, the pharmacological and toxicological properties, the anticancer activity, and the mechanisms of action of CPX and its derivatives as anticancer agents. METHODS: PubMed and Google using the keywords "ciclopirox", "cancer or tumor" and "patent" were searched, and the identified literature was reviewed. RESULTS: Pharmacological and toxicological profiles from preclinical and clinical studies support that systemic administration of CPX and its derivatives is feasible and safe for cancer treatment. CPX exerts its anticancer activity by inhibiting cell proliferation, inducing apoptosis, suppressing cell migration and invasion, and inhibiting angiogenesis and lymphangiogenesis. Mechanistically, CPX impacts the expression or activities of multiple signaling molecules or pathways, such as ribonucleotide reductase, Myc, DJ-1, Wnt/ß-catenin, DOHH/eIF5A/PEAK1, VEGFR-3/ERK1/2, ATR/Chk1/Cdc25A, and AMPK/TSC/mTORC1. Most of these effects are attributed to iron chelation by CPX. Five patents have been retrieved: four patents on the development of CPX prodrugs to improve the water solubility and bioavailability of CPX, and one patent on the methods of bladder cancer treatment with CPX, CPX-O, or a CPX prodrug. CONCLUSION: CPX has a great potential to be repositioned for cancer therapy.
Asunto(s)
Antineoplásicos/farmacología , Ciclopirox/farmacología , Neoplasias/tratamiento farmacológico , Animales , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Antifúngicos/farmacología , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Disponibilidad Biológica , Proliferación Celular/efectos de los fármacos , Ciclopirox/administración & dosificación , Ciclopirox/efectos adversos , Reposicionamiento de Medicamentos , Humanos , Neoplasias/patología , Patentes como Asunto , SolubilidadRESUMEN
Topical onychomycosis therapy is commonly prescribed due to its tolerability and low incidence of side effects. There are limited data on adverse events associated with the newer topical onychomycosis drugs. The objectives of this study is to classify the most common adverse reactions associated with ciclopirox 8% solution, efinaconazole 10% solution, and tavaborole 5% solution. The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for the most common adverse reactions associated with ciclopirox 8% solution, efinaconazole 10% solution, and tavaborole 5% solution. Google Trends was used to examine public interest in these drugs and these data were compared with yearly adverse events in the FAERS database. The most common adverse reactions associated with ciclopirox 8% solution, efinaconazole 10% solution, and tavaborole 5% solution were drug ineffectiveness. Application site erythema and nail discoloration were reported with all three medications. Increased Google searches for efinaconazole and tavaborole were associated with increased in reporting of adverse events to the FDA. Topical antifungals are safe alternatives for patients who have contraindications to oral medications. For improved efficacy, physicians should confirm the diagnosis of onychomycosis and choose appropriate candidates before starting topical therapy. Patients should be given clear instructions on drug usage and counseled about the more common side effects, including application site reactions and nail discoloration.
Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Antifúngicos/efectos adversos , Onicomicosis/tratamiento farmacológico , United States Food and Drug Administration/estadística & datos numéricos , Administración Tópica , Compuestos de Boro/administración & dosificación , Compuestos de Boro/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Ciclopirox/administración & dosificación , Ciclopirox/efectos adversos , Eritema/inducido químicamente , Eritema/epidemiología , Humanos , Uñas/efectos de los fármacos , Pigmentación/efectos de los fármacos , Estudios Retrospectivos , Soluciones , Insuficiencia del Tratamiento , Triazoles/administración & dosificación , Triazoles/efectos adversos , Estados UnidosRESUMEN
BACKGROUND: Seborrheic dermatitis (SD) is a very common inflammatory skin disease. It occurs in 1-3% of the population. The most supported pathogenetic theory links SD to dandruff via a common etiology, yeasts of the genus Malassezia. Ketoconazole and ciclopirox (CPX) shampoo are considered as the first line treatment of SD of the scalp. CPX is a broad-spectrum, hydroxypyridone-derived, synthetic antifungal agent with anti-bacterial, anti-inflammatory, and anti-oxidant properties. The aim of this study was to assess the efficacy and tolerability of 1% CPX shampoo in SD of the scalp. METHODS: A total of 40 patients, 31 men and 9 women, mean age 33±6 years, with scalp SD of moderate-to-severe grade were enrolled, after their informed consent, in this 12-week prospective assessor-blinded trial. One-percent CPX shampoo (5 mL) was applied twice a week for 12 weeks. The primary efficacy parameter was the Total Dandruff Severity Score (TDSS), based on 4-point ordinal scales describing signs and symptoms (scaling, inflammation, and itching) of the disease, evaluated in an assessor-blinded fashion, at baseline and after 6 and 12 weeks. Secondary outcomes were the single items of the TDSS and the evaluation of local tolerability. RESULTS: At baseline the TDSS was 17±5. After 1% CPX TDSS was reduced to 10±5 at week 6 and to 6.6±4 at the end of study period (P=0.0001; ANOVA test). This difference represents a 62% reduction in comparison with baseline. At week 12, the reduction of scaling, inflammation and itching scores were -55%, -65%, and -69%, respectively. The product was very well tolerated. No side effects were reported or observed during the study. CONCLUSIONS: The study supports the use of 1% CPX shampoo in the treatment of SD of the scalp. CPX shampoo was able to reduce desquamation, inflammation and itching associated with scalp SD. Furthermore, 1% CPX shampoo was found to be safe and well tolerated.
Asunto(s)
Antifúngicos/administración & dosificación , Ciclopirox/administración & dosificación , Dermatitis Seborreica/tratamiento farmacológico , Preparaciones para el Cabello , Adulto , Antifúngicos/efectos adversos , Ciclopirox/efectos adversos , Femenino , Humanos , Masculino , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Método Simple Ciego , Resultado del TratamientoRESUMEN
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