title: Transungual delivery of efinaconazole: its deposition in the nail of onychomycosis patients and in vitro fungicidal activity in human nails.
abstract: BACKGROUND
  Effective transungual delivery of topical antifungal agents in onychomycosis has been hampered by poor nail permeation. To be effective they must have antifungal efficacy, and effectively permeate through the dense keratinized nail plate to the site of infection in the nail bed and nail matrix. The therapeutic efficacy of efinaconazole topical solution, 10% has been established in two phase 3 clinical trials in distal lateral subungual onychomycosis.
  
  
  OBJECTIVE
  To investigate the transungual delivery of efinaconazole in onychomycosis patients and its fungicidal activity in the toenail.
  
  
  METHODS
  Concentrations of efinaconazole were determined as part of a multi-center, open label study in forty onychomycosis patients following repeated application of efinaconazole topical solution, 5% and 10% to the toenails over 28 days, with a 2-week follow-up. Fungicidal activity against T. rubrum in the ventral layer of human nails was determined using an in vitro human nail infection model (ChubTur®).
  
  
  RESULTS
  Efinaconazole concentrations in the nail were four orders of magnitude higher than MIC values of efinaconazole against dermatophytes. Further, nail drug concentrations were not influenced by the presence of disease or nail thickness, and maintained at high antifungal levels post-treatment. Efinaconazole was effective in reducing fungal viability, suggesting that sufficient amounts of efinaconazole were being delivered into the ventral layer of the nail plate.<BR />
  
  
  CONCLUSIONS
  Effective transungual delivery of efinaconazole was demonstrated. The high efinaconazole concentrations in patient toenails and fungicidal activity in vitro potentially contribute to the clinical efficacy reported in phase 3 studies.
authors.forename: Misao
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Noriaki
authors.initials: N
authors.lastname: Sugimoto
authors.forename: Hideki
authors.initials: H
authors.lastname: Kawabata
authors.forename: Eiko
authors.initials: E
authors.lastname: Yamakawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kodera
authors.forename: Radhakrishnan
authors.initials: R
authors.lastname: Pillai
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tatsumi
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005260:Female; D005500:Follow-Up Studies; D005533:Foot Dermatoses / Q000188:drug therapy*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009262:Nails / Q000378:metabolism / Q000382:microbiology; D014009:Onychomycosis / Q000188:drug therapy* / Q000382:microbiology; D010539:Permeability; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014249:Trichophyton / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C431707:efinaconazole