Tolerance and kinetic behavior after single and repeated vaginal administration of sertaconazole cream and tablets in healthy volunteers

Sertaconazole is a new imidazole derivative that has been shown to have wide in vitro activity, particularly against dermatophytes and Candida albicans. Experimental studies inducing vaginal candidiasis in mice have shown that sertaconazole 2% cream is more active than miconazole 2% cream. The aim of our study was to evaluate vaginal and systemic tolerance of sertaconazole administered in two formulations (cream 2% and vaginal tablets 500 mg). The cream was applied in a single dose followed by a multiple administration twice daily for seven days. Vaginal tablets were given in a single dose. All studies were performed following a double-blind, crossover, randomized, and placebo-controlled design. Twelve women were involved in the study during three consecutive menstrual cycles, leaving appropriate washout periods between treatments. The variables assessed at various times were: subjective evaluations of vaginal discomfort by means of ten visual analogue scales (VAS-100 mm) and a questionnaire with 18 suggested side effects; a pharmacologic safety profile, including blood pressure, heart rate, electrocardiogram, body temperature, biochemical and hematological analysis; and systematic gynecologic examinations including vaginal mucus and fluid evaluations, pH, Papanicolaou smear, and colposcopy. Additionally, blood, vaginal fluid, and urine samples were collected to determine drug levels by means of a high-performance liquid chromatography method with ultraviolet detection. The clinical parameters measured showed no differences between cream or tablets and placebo. Overall results indicate that sertaconazole in both formulations displays a good local and systemic tolerance. Sertaconazole in plasma was not detected. Erratic levels were found in urine, probably due to contamination. Sertaconazole levels in high concentrations persisted in vaginal fluid for over 72 hours, supporting the potential clinical usefulness of this new drug in antifungal therapy.