Evaluation of Topical Antifungals Using a New Predictive Animal Model for Efficacy against Severe Tinea Unguium: A Comparison of Efinaconazole and Luliconazole

Mycopathologia. 2022 Dec;187(5-6):481-489. doi: 10.1007/s11046-022-00664-3. Epub 2022 Sep 12.

Abstract

Development of new topical drugs requires an animal onychomycosis model that can predict the drug efficacy against moderate to severe human onychomycosis because the severity of onychomycosis varies and affects the drug efficacy. This study established a non-immunosuppressive guinea pig tinea unguium model under 8-week infection condition in addition to a previously reported model under 4-week infection condition. In the tinea unguium model, most fungi were tightly present in the arthrospore form, like in human onychomycosis. The topical formulations of efinaconazole and luliconazole, two azole class anti-onychomycosis drugs, were evaluated for their efficacy in these models. In the untreated group, the nail fungal burden in the 8-week model was higher than that in the 4-week model and the stronger infection intensity affected the efficacy of the drugs, suggesting that the 8-week model was more severe. The 90% efficacy rate (42%) of luliconazole in the 8-week model was significantly lowered than that (83%) in the 4-week model, and its 99% efficacy rates were 0% in both models. Conversely, the 90% and 99% efficacy rates of efinaconazole (92% and 50% in the 4-week model, and 75% and 25% in the 8-week model, respectively) were not significantly different between the two infection durations. In addition, efinaconazole was more effective than luliconazole in reducing the nail fungal burden. Considering the relevance of clinical reports of the effectiveness of efinaconazole on severe onychomycosis, the new severe tinea unguium model would predict drug efficacy against moderate to severe onychomycosis.

Keywords: Arthrospore; In vivo model; Mycology; Severe onychomycosis; Topical antifungal drug.

MeSH terms

  • Administration, Topical
  • Animals
  • Antifungal Agents / therapeutic use
  • Disease Models, Animal
  • Guinea Pigs
  • Humans
  • Onychomycosis* / drug therapy
  • Onychomycosis* / microbiology

Substances

  • efinaconazole
  • Antifungal Agents
  • luliconazole