The study aims to evaluate the tolerability of multiple-dose
topical dapaconazole tosylate, a new imidazole antifungal drug, in healthy volunteers.
Twenty-four healthy volunteers (12 men) with skin pigmentation classified as
I-III in the Fitzpatrick scale enrolled in this open-label, two-treatment study
with daily application of 40 mg of dapaconazole for 14 consecutive days. Drug
application was monitored by a physician and photographs were taken before and
1 h after application to evaluate possible dermatological reactions. Medical
evaluations including physical examination, laboratory tests and electrocardiograms
were performed to evaluate possible systemic adverse events. To evaluate systemic
dapaconazole absorption blood samples were collected before and 2, 4 and 6 h
after products application on the first day of treatment. The same occurred
in days 7 and 13, but an extra 24 h sample was collected after application of
the products. Dapaconazole plasma levels were measured by high-performance liquid
chromatography coupled to tandem mass spectrometry. No volunteers had dermatological
reactions to the formulations. Only one blood sample had detectable levels of
dapaconazole (0.23 ng mL-1). One volunteer presented hypertriglyceridemia
(424 mg dL-1) after the 14 days of treatment. Three months after
the last dose triglycerides were back to normal range (151 mg dL-1).
Dapaconazole 2% (Zilt®) showed a safe adverse event profile for topical
application in daily doses of 40 mg for up to 14 days in healthy individuals.
T. Gagliano-Juca, A.M.M. Arruda, M.F. Sampaio, A.G. Lopes and G. De Nucci, 2014. Phase I Study of the Novel Antifungal Agent Dapaconazole (Zilt®)
in Healthy Volunteers. International Journal of Pharmacology, 10: 507-512.