title: Eberconazole cream: topical and general tolerability, sensitisation potential, and systemic availability.
abstract: Eberconazole is a topical imidazole derivative, which has shown high potency against dermatophytes and yeasts (several species of Candida, Malassezia) in vitro and in experimental models. Clinical trials have found that the compound has a high degree of efficacy against dermatophytes and good tolerability. Evaluation of its a) topical and general tolerability, b) eventual development of sensitisation, c) local availability, and d) degree of systemic absorption. Two clinical trials with 28 healthy young volunteers of both sexes were performed. In Study I, placebo or eberconazole cream (2%) were applied at increasing doses: day 1 (0.5 g), days 2-3 (1 g), days 4-5 (2 g), days 6-7 (4 g), days 8-9 (8 g), and days 10-11 (12 g). On day 1, each application area was washed with ethanol-soaked gauzes at different times to assess availability of the active compound. In Study II, eberconazole cream (1%) was applied on day 1 and again at least one week later. After the first application, blood and urine samples were obtained at different times to assess systemic absorption. The only change observed was slight redness in a few volunteers after both active and placebo applications. This remitted spontaneously without intervention and we were able to continue with the administration of repeated increasing-doses. A few participants described side effects; these were all of mild intensity, and occurred in areas where placebo or eberconazole were applied, mainly within the first hour postapplication. The most frequent effect after the first application was coldness, and after repeated increasing-doses there was itching. No signs or symptoms of skin reactivity were observed following reexposure to the product. No clinically relevant changes were observed in vital signs (systolic and diastolic blood pressure, heart rate, body temperature), ECG, or analytical parameters (clinical haematology and biochemistry). The quantity of compound collected through washing gauzes decreased progressively over time. Plasma and urine concentrations of eberconazole were below the quantification limit of the analytical method (5 ng/ml) at all times. Eberconazole cream is a topical antimycotic drug that has good local and general tolerability. It has acceptable topical availability, no detectable systemic drug levels, and does not appear to cause skin sensitivity.
authors.affiliation: Centre d'Investigacio de Medicaments, Institut de Recerca, Servei de Farmacologia Clinica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. mbarbanoj@hsp.santpau.es
authors.forename: M-J
authors.initials: MJ
authors.lastname: Barbanoj
authors.forename: R
authors.initials: R
authors.lastname: Antonijoan
authors.forename: C
authors.initials: C
authors.lastname: García-Gea
authors.forename: M
authors.initials: M
authors.lastname: Puntes
authors.forename: I
authors.initials: I
authors.lastname: Gich
authors.forename: F
authors.initials: F
authors.lastname: Jané
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001682:Biological Availability; D003508:Cycloheptanes / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004342:Drug Hypersensitivity / Q000209:etiology; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D012869:Skin Absorption
chemical_list: D000935:Antifungal Agents; D003508:Cycloheptanes; D007093:Imidazoles; C118963:eberconazole