Potential of Ravuconazole and its Prodrugs as the New OralTherapeutics for Onychomycosis

Onychomycosis is a fungal infection of the nail apparatus caused by dermatophytes, Candida and non-dermatophytic molds. It is highly prevalent in the general population worldwide and also responsible for significant morbidity and complications and does not usually cure itself. Thus, the condition needs to be treated in view of physical and psychological problems produced. Currently, oral medications using terbinafine are the most effective therapy, but it has relatively limited therapeutic success, particularly for long-term management. Such existing oral therapies are associated with high recurrence rates and treatment failure, as well as with potential adverse events and drug-drug interactions. In the light of these issues, development of more efficacious and safer alternatives for the treatment of onychomycosis is warranted.Ravuconazole and its prodrugs are promising new drug candidates for oral therapy of onychomycosis, among which a water-soluble prodrug, mono-lysine phosphoester derivative (E1224 or BFE1224) is in the most advanced stage of clinical development; a Phase II dose-finding study has been successfully completed and Phase III comparative studies are in progress in Japan.This review aims to summarize our current status of knowledge and information on ravuconazole and its prodrugs, particularly BFE1224, as the potential oral treatment option for onychomycosis. It also summarize the clinical features of onychomycosis with particular stress on its etiology, epidemiology, and current therapeutic options and their limitations. Given its clinical usefulness, BFE1224 may become a valuable addition to the current armamentarium for the treatment of onychomycosis.