Ciclopirox Nail Lacquer 8%: In vivo Penetration into and through Nails and in vitro Effect on Pig Skin

Abstract

This report presents original methods to assess the bioavailability of an antifungal drug from a varnish preparation in finger nails. For the studies with human volunteers a ciclopirox 8 % nail lacquer was used to determine its efficacy in the treatment of onychomycoses. In vivo studies were performed on the fingernails of healthy volunteers by determining the total amount of ciclopirox penetrated per milligram of nail and the partition of the drug in the plate of the nails (technically divided into four layers). Ciclopirox concentrations were evaluated by measuring the inhibition of Candida pseudotropicalis growth in vitro. The ciclopirox concentration after 30 days treatment was determined as 3.35 ± 0.82 µg/mg nail material. This is a sufficient amount to kill the fungal pathogens. In addition, in vitro penetration experiments were carried out with excised pig skin. Lacquer formulations from 0.5 to 8 % were used to inhibit the growth of Trichophyton mentagrophytes. Formulations from 2 to 8% led to a strong to total inhibition of the dermatophyte after 30 min treatment time.

Action mechanisms of modern antifungal agents and resulting problems in the management of onychomycosis

“…The MIC of terbinafine for the major dermatophytes range between 0.001 and 0.06 μ g ml −1 13 . The mean drug concentrations on day 8 after a daily dose of 250 mg terbinafine given for 7 days to eight healthy volunteers were determined in the following tissue compartments: 14 plasma, 1.01 μ g ml −1 ; sebum, 5.18 μ g g −1 ; stratum corneum, 1.63 μ g g −1 ; hair, 1.05 μ g g −1 and nails, 0.52 μ g g −1 . The ratio of MIC to tissue level showed that the concentration of terbinafine in all relevant tissues is 100–1000 times higher than the MIC of the pathogenic dermatophytes.…”

Nail biology and nail science

“…When amorolfine is applied to nail, its penetration is enhanced by pretreatment with DMSO and the penetration is further enhanced if methylene chloride is used as a vehicle for the antifungal in preference to ethanol [217]. Some medicated lacquers are also able to penetrate sufficiently to be of clinical use, particularly if their access is increased by abrading the dorsal surface of the nail plate [218, 219]. The concentration gradient, and hence diffusion, can be increased further by facilitating solution of the reagents, such as miconazole, by lowering the pH [220].…”

Activity of TDT 067 (Terbinafine in Transfersome) against Agents of Onychomycosis, as Determined by Minimum Inhibitory and Fungicidal Concentrations

“…A multicenter study of 456 patients demonstrated a 54% clinical response rate for amorolfine nail lacquer; however, patients in this study had no nail bed involvement (27). Ciclopirox, the only FDA-approved topical agent for the treatment of onychomycosis in the United States, achieves drug concentrations in the nail considerably higher than the MIC of ciclopirox for dermatophytes (5). However, poor clinical cure rates have been reported in United States-based studies (Ͻ10% complete cure) (16).…”