title: Safety and tolerability of luliconazole solution 10-percent in patients with moderate to severe distal subungual onychomycosis.
abstract: The study objective was to evaluate the safety, tolerability, systemic exposure, and pharmacokinetics (PK) of 10% luliconazole solution (luliconazole) when topically applied once daily to all 10 toenails and periungual areas in patients with moderate to severe distal subungual onychomycosis. In this single-center, open-label study, 24 patients applied 20 mg/ml of luliconazole (twice the clinical dose) for 29 days with a 7-day follow-up. Complete PK profiles were determined on days 1, 8, 15, and 29. Safety/tolerability assessments included application site reactions, adverse events, vital signs, clinical laboratory findings, and electrocardiograms. Mean luliconazole plasma concentrations remained around the lower limit of quantitation (0.05 ng/ml) and were comparable on days 8, 15, and 29 (range, 0.063 to 0.090 ng/ml), suggesting steady state occurred by day 8. Every patient had undetectable plasma luliconazole levels for at least 11% of the time points, and 12 of the 24 patients had undetectable levels for at least 70% of the time points. The maximum plasma concentration of luliconazole (C(max)) observed in any patient was 0.314 ng/ml and the maximum area under the concentration-time curve from 0 to 24 h (AUC0-24) was 4.34 ng · h/ml. Five patients (21%) had measureable luliconazole levels in the plasma 7 days after the last dose. The median concentration of luliconazole in the nail at this time point was 34.65 mg/g (from 42 of 48 collected toenail samples). There was one mild incidence of skin erythema on day 5 that resolved on day 8, there were no reports of drug-induced systemic side effects, and there was no evidence of QT prolongation. Luliconazole, when applied once daily to all 10 fungus-infected toenails for 29 days, is generally safe and well tolerated and results in significant accumulation of drug in the nail. Systemic exposure is very low, with no evidence of drug accumulation.
authors.affiliation: J & S Studies, Inc, College Station, Texas, USA.
authors.forename: T
authors.initials: T
authors.lastname: Jones
authors.forename: A
authors.initials: A
authors.lastname: Tavakkol
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009262:Nails / Q000187:drug effects / Q000382:microbiology; D014009:Onychomycosis / Q000188:drug therapy* / Q000382:microbiology; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D019999:Pharmaceutical Solutions; C112528:luliconazole
references.citation: Am J Clin Dermatol. 2011 Oct 1;12(5):313-20
references.pmid: 21834596
references.citation: J Clin Pharm Ther. 2010 Oct;35(5):497-519
references.pmid: 20831675
references.citation: J Am Acad Dermatol. 2007 Jun;56(6):939-44
references.pmid: 17307276
references.citation: J Dtsch Dermatol Ges. 2009 Jan;7(1):11-9, 11-20
references.pmid: 18479501
references.citation: Mycopathologia. 2008 Nov-Dec;166(5-6):353-67
references.pmid: 18478357
references.citation: Acta Derm Venereol. 2007;87(3):255-9
references.pmid: 17533493
references.citation: Ther Clin Risk Manag. 2005 Dec;1(4):299-306
references.pmid: 18360572
references.citation: J Infect Chemother. 2006 Jun;12(3):163-5
references.pmid: 16826352
references.citation: Am J Clin Dermatol. 2000 Jan-Feb;1(1):19-26
references.pmid: 11702301
references.citation: Med Mycol. 2009;47(6):640-7
references.pmid: 19115136
references.citation: Clin Microbiol Rev. 1998 Jul;11(3):415-29
references.pmid: 9665975
references.citation: Antimicrob Agents Chemother. 2012 Jun;56(6):3138-43
references.pmid: 22391525
references.citation: J Infect Chemother. 2004 Aug;10(4):216-9
references.pmid: 15365862
references.citation: Dermatol Ther. 2007 Jan-Feb;20(1):31-46
references.pmid: 17403258
references.citation: J Drugs Dermatol. 2010 Sep;9(9):1109-13
references.pmid: 20865843
references.citation: J Am Podiatr Med Assoc. 2000 Nov-Dec;90(10):491-4
references.pmid: 11107709