{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:08:17Z","timestamp":1793689697700,"version":"4.5.1"},"reference-count":12,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,5,3]],"date-time":"2005-05-03T00:00:00Z","timestamp":1115078400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acad Dermatol Venereol"],"published-print":{"date-parts":[[2005,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> To determine the effectiveness and safety of ravuconazole in the treatment of toenail onychomycosis.<\/jats:p><jats:p><jats:bold>Design\u2002<\/jats:bold> A phase I\/II randomized, double\u2010blind, double\u2010dummy, placebo\u2010controlled, dose\u2010ranging study. Four 12\u2010week dosing regimens were used: 200\u00a0mg\/day; 100\u00a0mg\/week; 400\u00a0mg\/week and placebo. Subjects returned at weeks 2, 4, 6, 8, 10, 12, 14, 16, 24, 36 and 48 for assessment. Subjects were enrolled at 10 dermatology practices (seven in the United States, one in Canada, two in France).<\/jats:p><jats:p><jats:bold>Subjects\u2002<\/jats:bold> Adults with distal subungual onychomycosis of one great (hallux) toenail (minimum area of 25%), and at least 2\u00a0mm of proximal nail clear of disease were selected. Onychomycosis was confirmed by direct microscopy and\/or fungal culture. Subjects with conditions known to produce abnormal\u2010appearing nails were excluded. One hundred and fifty\u2010one subjects were randomized in a 2\u00a0:\u00a02\u00a0:\u00a02\u00a0: 1 ratio to the treatments above.<\/jats:p><jats:p><jats:bold>Main Outcome Measures\u2002<\/jats:bold> Primary efficacy was the effective cure rate at week 48 (mycological cure, and clinical cure or\u00a0&gt;\u00a030% improvement).<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Effective cure was found in 56% of subjects using 200\u00a0mg\/day. Effective cure was 10% in subjects receiving 100\u00a0mg\/week, 8% of subjects using 400\u00a0mg\/week, and 15% of subjects using placebo. Mycological cure was seen in 59% of subjects in the 200\u2010mg\/day group, which was significantly higher than the rates found in the other groups. Drug\u2010related adverse events were infrequent in all treatment arms. Headache was the most frequently reported event. Abnormal laboratory tests were infrequent over the 12\u00a0weeks of dosing. Abnormal laboratory findings with increases beyond normal of Grade 2, 3 or 4 were found in 8\/148 subjects (5.4%). Only the 200\u00a0mg daily regimen had a mean plasma steady state concentration of ravuconazole exceeding the MIC<jats:sub>90<\/jats:sub> adjusted for 98% protein binding (3000\u00a0ng\/mL).<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> For the treatment of onychomycosis, ravuconazole 200\u00a0mg\/day for 12\u00a0weeks is the most effective of the regimens investigated. The safety of all regimens was acceptable. The concentrations of ravuconazole in the plasma compared to the adjusted MIC<jats:sub>90<\/jats:sub> may be useful in predicting the clinical and mycologic response of therapy.<\/jats:p>","DOI":"10.1111\/j.1468-3083.2005.01212.x","type":"journal-article","created":{"date-parts":[[2005,6,29]],"date-time":"2005-06-29T11:12:31Z","timestamp":1120043551000},"page":"437-443","source":"Crossref","is-referenced-by-count":61,"title":["A phase I\/II randomized, double\u2010blind, placebo\u2010controlled, dose\u2010ranging study evaluating the efficacy, safety and pharmacokinetics of ravuconazole in the treatment of onychomycosis"],"prefix":"10.1111","volume":"19","author":[{"given":"AK","family":"Gupta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Leonardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"RR","family":"Stoltz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"PF","family":"Pierce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B","family":"Conetta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Ravuconazole onychomycosis group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,5,3]]},"reference":[{"issue":"10","key":"e_1_2_5_2_2","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1128\/AAC.40.10.2243","article-title":"Efficacy of ER\u201030346, a novel oral triazole antifungal agent, in experimental models of aspergillosis, candidiasis, and cryptococcosis","volume":"40","author":"Hata K","year":"1996","journal-title":"Antimicrob Agents Chemother"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0732-8893(99)00063-2"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.2.441-443.2000"},{"key":"e_1_2_5_5_2","unstructured":"BregaEF GonzalezG FothergillWet al.Anin vitroevaluation of new triazole antifungal agents against clinical isolates of dermatophytes in comparison with terbinafine itraconazole and fluconazole. Abstract 841. Page 23.40th Interscience Conference on Antimicrobial Agents and Chemotherapy.Toronto Canada September 1720 2000."},{"key":"e_1_2_5_6_2","unstructured":"GraselaDM OlsenSJ MummanenVet al.Ravuconazole: multiple ascending oral dose study in healthy subjects. Abstract 839 Page 22.40th Interscience Conference on Antimicrobial Agents and Chemotherapy.Toronto CanadaSeptember 1720 2000."},{"key":"e_1_2_5_7_2","unstructured":"MummaneniV GeraldesM HadjilambrisOWet al.Effect of ravuconazole on the pharmacokinetics of simvastatin in healthy subjects. Abstract 841 Page 23.40th Interscience Conference on Antimicrobial Agents and Chemotherapy.Toronto CanadaSeptember 1720 2000."},{"key":"e_1_2_5_8_2","unstructured":"MarinoMR MummaneniV NortonJet al.Ravuconazole exposure\u2010response relationship in HIV+ patients with oropharyngeal candidiasis.41st ICAAC.Abstracts. Chicago Illinois September 2225 2001."},{"key":"e_1_2_5_9_2","unstructured":"OlsenAJ RolanP MummaneniVet al.Ravuconazole: multiple ascending oral dose study in healthy subjects. Abstract 838. Page 22.40th Interscience Conference on Antimicrobial Agents and Chemotherapy.Toronto Canada September 1720 2000."},{"key":"e_1_2_5_10_2","unstructured":"Lamisil\u00ae (terbinafine hydrochloride tablets) Prescribing Information. 2001. Novartis. Revised October 2001."},{"key":"e_1_2_5_11_2","unstructured":"Sporonox\u00ae (itraconazole) capsules \u2013 Prescribing Information. 2001. Janssen. Revised January 2003."},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.4.1032-1037.2002"},{"key":"e_1_2_5_13_2","unstructured":"National Committee for Clinical Laboratory Standards: Reference Method for Broth Dilution Antifungal Susceptibility Testing for Yeasts M27\u2010A. January 29 1997."}],"container-title":["Journal of the European Academy of Dermatology and Venereology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1468-3083.2005.01212.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1468-3083.2005.01212.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T02:22:58Z","timestamp":1695867778000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1468-3083.2005.01212.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5,3]]},"references-count":12,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2005,7]]}},"alternative-id":["10.1111\/j.1468-3083.2005.01212.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1468-3083.2005.01212.x","archive":["Portico"],"relation":{},"ISSN":["0926-9959","1468-3083"],"issn-type":[{"value":"0926-9959","type":"print"},{"value":"1468-3083","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5,3]]}}}