{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T19:00:35Z","timestamp":1776970835352,"version":"3.51.4"},"reference-count":40,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2018,1,1]],"date-time":"2018-01-01T00:00:00Z","timestamp":1514764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            ME1111 is a novel antifungal agent currently under clinical development as a topical onychomycosis treatment. A major challenge in the 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. An ME1111 solution and other launched topical formulations were applied to an\n            <jats:italic>in vitro<\/jats:italic>\n            dose model for 14 days based on their clinical dose and administration. Drug concentrations in the deep layer of the nail and within the cotton pads beneath the nails were measured using liquid chromatography-tandem mass spectrometry. Concentrations of ME1111 in the 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\n            <jats:sub>90<\/jats:sub>\n            value against\n            <jats:named-content content-type=\"genus-species\">Trichophyton rubrum<\/jats:named-content>\n            (\n            <jats:italic>n<\/jats:italic>\n            = 30). Unlike other drugs, the\n            <jats:italic>in vitro<\/jats:italic>\n            antifungal activity of ME1111 was not affected by 5% human keratin and under a mild acidic condition (pH 5.0). The\n            <jats:italic>in vitro<\/jats:italic>\n            antidermatophytic efficacy coefficients (ratio of free drug concentration to MIC\n            <jats:sub>90<\/jats:sub>\n            s against\n            <jats:named-content content-type=\"genus-species\">T. rubrum<\/jats:named-content>\n            ) of ME1111, as measured in deep nail layers, were significantly higher than those of efinaconazole, tavaborole, ciclopirox, and amorolfine (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.05). This suggests that ME1111 has excellent permeation of human nails and, consequently, the potential to be an effective topical onychomycosis treatment.\n          <\/jats:p>","DOI":"10.1128\/aac.00779-17","type":"journal-article","created":{"date-parts":[[2017,10,30]],"date-time":"2017-10-30T15:50:32Z","timestamp":1509378632000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":19,"title":["<i>In Vitro<\/i>\n            Human Onychopharmacokinetic and Pharmacodynamic Analyses of ME1111, a New Topical Agent for Onychomycosis"],"prefix":"10.1128","volume":"62","author":[{"given":"Natsuki","family":"Kubota-Ishida","sequence":"first","affiliation":[{"name":"Meiji Seika Pharma Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naomi","family":"Takei-Masuda","sequence":"additional","affiliation":[{"name":"Meiji Seika Pharma Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaori","family":"Kaneda","sequence":"additional","affiliation":[{"name":"Meiji Seika Pharma Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Nagira","sequence":"additional","affiliation":[{"name":"Meiji Seika Pharma Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsubasa","family":"Chikada","sequence":"additional","affiliation":[{"name":"Meiji Seika Pharma Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Nomoto","sequence":"additional","affiliation":[{"name":"Meiji Seika Pharma Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuji","family":"Tabata","sequence":"additional","affiliation":[{"name":"Meiji Seika Pharma Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sho","family":"Takahata","sequence":"additional","affiliation":[{"name":"Meiji Seika Pharma Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazunori","family":"Maebashi","sequence":"additional","affiliation":[{"name":"Meiji Seika Pharma Co., Ltd., Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Hui","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, San Francisco, California, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard I.","family":"Maibach","sequence":"additional","affiliation":[{"name":"University of California, San Francisco, San Francisco, California, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.107754"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2000.104794"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.1995.tb02741.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004105"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.16.2.157"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2012.10.013"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-013-0152-x"},{"key":"e_1_3_2_9_2","first-page":"1124","article-title":"The efficacy and safety of tavaborole, a novel, boron-based pharmaceutical agent: phase 2 studies conducted for the topical treatment of toenail onychomycosis","volume":"13","author":"Toledo-Bahena ME","year":"2014","unstructured":"Toledo-Bahena ME, Bucko A, Ocampo-Candiani J, Herz-Ruelas ME, Jones TM, Jarratt MT, Pollak RA, Zane LT. 2014. 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