Antifungal ME1111 in vitro human onychopharmacokinetics

• Published in: Drug development and industrial pharmacy Vol. 43; no. 1; p. 22
• Main Authors: Hui, Xiaoying, Jung, Eui Chang, Zhu, Hanjiang, Maibach, Howard I
• Format: Journal Article
• Language: English
• Published: England 02.01.2017
• Subjects: Administration, Topical; Antifungal Agents - administration & dosage; Antifungal Agents - pharmacokinetics; Dose-Response Relationship, Drug; Foot Dermatoses - drug therapy; Foot Dermatoses - metabolism; Humans; Onychomycosis - drug therapy; Onychomycosis - metabolism; Phenols - administration & dosage; Phenols - pharmacokinetics; Pyrazoles - administration & dosage; Pyrazoles - pharmacokinetics; in vitro nail deep penetration; Antifungal agent – ME1111; antifungal efficacy; transungual kinetics; great toenail
• ISSN: 1520-5762
• DOI: 10.1080/03639045.2016.1201098

This study determined ME1111 onychopharmacokinetics and possible topical antifungals' clinical efficacy in human great toenails using an in vitro finite dose model. ME1111 topical formulations in 1, 5, 10 or 15% for 3 days observation and 1, 5 or 10% for 14 days observation, respectively, were used to determine ME1111 penetration rate and transungual kinetics. ME1111 concentrations in the deeper nail (ventral/intermediate layers) and a cotton pad/nail bed, were several orders of magnitude greater than MIC and MFC for three major dermatophytes. ME1111 concentrations 3 days after a single and 14 days after multiple dosing of 10% formulation were 253 and 7991 μg/g nail, respectively, and superior to those of 8% ciclopirox control. ME1111 concentration (μg equivalent/cm ) in the cotton pad following 10% ME1111 multiple applications increased linearly throughout the 336 h experiment and was significantly greater than that of 8% ciclopirox. Flux rate of ME1111 averaged as 50.9 μg/cm /day, which was ca. two orders of magnitude greater than the MIC values. The novel antifungal ME1111 penetrated well into human nail plate and its concentrations in the deeper nail and cotton pad after application of 10% formulation were significantly greater than those of ciclopirox.