Fosravuconazole L‐lysine ethanolate (F‐RVCZ) is a prodrug of ravuconazole, a novel triazole antifungal agent, exerting broad and potent antifungal activity. The efficacy and safety of F‐RVCZ, compared with a placebo, were investigated in a multicenter, double‐blind, randomized study of Japanese onychomycosis patients with 25% or more clinical involvement of the target toenail. Subjects (n = 153) were randomly assigned to receive F‐RVCZ (100 mg RVCZ, n = 101) or placebo (n = 52) p.o. once daily for 12 weeks. The primary end‐point was the rate of complete cure (clinical cure [0% clinical involvement of the target toenail] plus mycological cure [negative potassium hydroxide examination]) at week 48 (36‐week post‐treatment visit). Secondary end‐points were changes over time in the efficacy and mycological effect of F‐RVCZ. Safety was also evaluated. The complete cure rate at week 48 was significantly higher with F‐RVCZ (59.4%, 60/101) than the placebo (5.8%, 3/52) in the full analysis set (P < 0.001). The mycological cure rate at week 48 was also significantly higher with F‐RVCZ (82.0%, 73/89) than the placebo (20.0%, 10/50, P < 0.001). Regarding safety, adverse events were observed in 83.2% (84/101) and 80.8% (42/52), and adverse drug reactions (ADR) in 23.8% (24/101) and 3.8% (2/52) of F‐RVCZ and placebo subjects, respectively. ADR were mild to moderate in severity, with none being serious. F‐RVCZ (equivalent to 100 mg ravuconazole) administrated once daily for 12 weeks was more effective than placebo and tolerable in patients with onychomycosis, suggesting it to be a promising drug for onychomycosis treatment.

Onychomycosis is a highly prevalent and intractable disease. The first-line treatment agents are oral preparations, but an effective topical medication has long been desired. The objective was to investigate the efficacy and safety of luliconazole 5% nail solution, an imidazole antifungal agent, for the treatment of patients with onychomycosis. A multicenter, double-blind, randomized phase III study was conducted in Japanese patients with distal lateral subungual onychomycosis affecting the great toenails, with 20-50% clinical involvement. Patients were randomized (2:1) to luliconazole or vehicle once daily for 48 weeks. The primary end-point was the complete cure rate (clinical cure [0% clinical involvement of the nail] plus mycological cure [negative results on direct microscopy]). The adverse event incidence was monitored to evaluate safety. The complete cure rate significantly favored luliconazole (14.9%, 29/194 subjects) versus vehicle (5.1%, 5/99) (P = 0.012). Similarly, the negative direct microscopy rate was significantly higher with luliconazole (45.4%, 79/174) than with vehicle (31.2%, 29/93) (P = 0.026). There were no serious adverse drug reactions. We conclude that once daily topical luliconazole 5% nail solution demonstrated clinical efficacy and was confirmed to be well tolerated.

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Three cationic water-soluble chlorin e(6) derivatives, that is, 6a-,gammab-,7c-tris(2-trimethylammonioethyl)chlorin e(6) (1), 6a-,gammab-,7c-tris(3-methylpyridiniummethyl)chlorin e(6) (2), and 6a-,gammab-, 7c-tris(2-trimethylammonioethyl)-2-(3-trimethylammonioprop-1-enyl)chlorin e(6) (3), have been designed and synthesized to allow the study of their DNA-binding and -photocleavage activities. The DNA-unwinding assay, measurements of melting temperatures of double-stranded DNA, and the induced CD and visible absorption spectra have revealed that 1 and 3 are intercalated into the base pairs of the double-helical DNA, while 2 is bound to outside the minor groove of the double-helical DNA. The cationic water-soluble chlorin e(6) derivatives effectively cleave the double-helical DNA under photoirradiation and the DNA-photocleavage activity increases in the order 3>1>2. The DNA-binding and -photocleavage characteristics of the three cationic water-soluble chlorin e(6) derivatives are influenced by aspects of their molecular structure, such as the kind, number, and position of the cationic substituents.

This study evaluated the utility of combination of digoxin (0.25 mg) and rosuvastatin (5 mg) as a new transporter (P‐glycoprotein/breast cancer resistance protein/organic anion‐transporting polypeptide (OATP)1B1/OATP1B3) probe cocktail (Oita combination) for drug–drug interaction (DDI) studies by demonstrating lack of DDI of digoxin on the pharmacokinetics (PKs) of rosuvastatin, as it was already known that rosuvastatin did not affect digoxin PK. This was an open‐label, two‐period study in which the primary end points were the geometric mean ratio (GMR) of the area under the plasma rosuvastatin concentration‐time curve from time zero to last (AUC last) after rosuvastatin administration combined with digoxin to that after rosuvastatin administration alone and its 90% confidence interval (CI). As the GMR of AUC last was 0.974 and its 90% CI was 0.911–1.042, it was judged that digoxin does not affect rosuvastatin PK. Results of this study have rationalized utility of the Oita combination as a transporter probe cocktail for clinical DDI studies.