In Vitro Human Onychopharmacokinetic and Pharmacodynamic Analyses of ME1111, a New Topical Agent for Onychomycosis.

ME1111 is a novel antifungal agent currently under clinical development as a topical onychomycosis treatment. A major challenge in application of topical onychomycotics is penetration and dissemination of antifungal agent into the infected nail plate and bed. In this study, pharmacokinetic/pharmacodynamic parameters of ME1111 that potentially correlate with clinical efficacy were compared with those of marketed topical onychomycosis antifungal agents: efinaconazole, tavaborole, ciclopirox, and amorolfine. ME1111 solution and other launched topical formulations were applied to an in vitro dose model for 14 days based on their clinical dose and administration. Drug concentration in deep layer of the nail and within the cotton pads beneath the nails were measured using liquid chromatography-mass spectrometry. Concentration of ME1111 in nail and cotton pads were much higher than those of efinaconazole, ciclopirox, and amorolfine. Free drug concentrations of ME1111 in deep nail layers and cotton pads were orders of magnitude higher than the MIC 90 value against Trichophyton rubrum (n = 30). Unlike other drugs, in vitro antifungal activity of ME1111 was not affected by 5% human keratin and mild acidic conditions (pH 5.0). The in vitro anti-dermatophytic efficacy coefficient (ratio of free drug concentration to MIC 90 s against T. rubrum ) of ME1111, as measured in deep nail layers, was significantly higher than that of efinaconazole, tavaborole, ciclopirox, and amorolfine ( p