Nail penetration of sertaconazole with a sertaconazole-containing nail patch formulation.

ABSTRACT

BACKGROUND AND OBJECTIVE: Sertaconazole, an imidazole antifungal drug, has been proven to have broad and potent antifungal activity. In the present study, the pharmacokinetics of sertaconazole nail patches, developed for treatment of onychodystrophy and onychomycosis, were investigated in healthy volunteers. The objective of the study was to investigate the penetration of sertaconazole into the nail and plasma and the residual sertaconazole concentration in patches after 1 week of application onto the nails. METHODS: In a double-blind study, 16 healthy adults were treated with a 2.2 cm2 nail patch containing sertaconazole 3.63 mg and another patch containing no antifungal agent, which were placed on the left and right thumbnail of each subject, respectively (or vice versa), in a randomized order. The treatment period was 6 weeks and the patches were replaced weekly. Nail clippings, used nail patches, and blood samples were investigated to determine sertaconazole concentrations. RESULTS: Sertaconazole was detected in all sertaconazole-treated nail samples with mean concentrations of >100 microg/g, which exceeds the minimum inhibitory concentrations (MICs) for all relevant fungi in this context. Measurements of the residual dose in the patches suggested that 16-71% of the active ingredient had penetrated into the nail. No plasma sertaconazole concentrations could be detected. CONCLUSION: By virtue of their positive influence (occlusion) on water and lipid metabolism in dystrophic nails, nail patches should have beneficial therapeutic effects in onychodystrophic conditions. Addition of the antifungal agent sertaconazole adds broad-spectrum antimicrobial activity. In this study, the concentrations of sertaconazole in the nails were shown to be well above the MIC values for pathogenic fungi relevant to onychomycosis. No systemic absorption of the active ingredient was detectable, which should exclude unwanted systemic effects of the drug.