Drug properties of fosravuconazole L-lysine ethanolate (NAILIN® Capsules 100 mg), a new oral azole therapeutic for onychomycosis: an analysis based on non-clinical and clinical trial data
Autor: | Yuto Aoki, Hideyo Yamaguchi, Makoto Nakano |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Pharmacology Drug chemistry.chemical_classification business.industry media_common.quotation_subject Prodrug Ravuconazole Bioavailability 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Pharmacokinetics Tolerability chemistry Oral administration Medicine Azole business 030217 neurology & neurosurgery media_common |
Zdroj: | Folia Pharmacologica Japonica. 153:79-87 |
ISSN: | 1347-8397 0015-5691 |
Popis: | Ravuconazole is a fourth generation azole exerting strong antifungal activity, with low drug-drug interaction and hepatic dysfunction risks. Fosravuconazole l-lysine ethanolate (fosravuconazole; NAILIN® Capsules 100 mg) was developed as a ravuconazole prodrug. Ravuconazole exerts strong antifungal activity against various pathogenic fungi including dermatophytes and Candida. Through prodrug formation, pharmacokinetic improvement was achieved, and bioavailability after oral administration reached 100%. The plasma ravuconazole concentration became 10-35 times higher than with current oral anti-onychomycosis drugs, and showed good skin and nail tissue transition plus tissue retention. This improvement obtained with fosravuconazole reflects its superior pharmacokinetic properties. We conducted a clinical trial with fosravuconazole orally administered once a day (100 mg ravuconazole) for 12 weeks in Japanese onychomycosis patients. The ravuconazole concentration in nail tissues exceeded the MIC90 against dermatophytes, even after treatment completion. Furthermore, the placebo-controlled, double-blind, comparative trial showed significantly superior effects (at 48 weeks after starting treatment, with a complete cure rate of 59.4%, a marked clinical improvement rate of 83.1%, and a mycological cure rate by direct microscopy of 82.0%). The major adverse reactions were laboratory abnormalities and gastrointestinal disorders with no severe symptoms, suggesting good tolerability. Fosravuconazole has fewer drug-drug interactions, is not affected by food, and is also expected to improve medication adherence since the administration period is only 12 weeks and there is no drug-free period as required with pulse therapy. Thus, fosravuconazole has many favorable pharmacological properties and can reasonably be expected to become a new oral treatment option for onychomycosis. |
Databáze: | OpenAIRE |
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