Access of Efinaconazole Topical Solution, 10%, to the Infection Site by Spreading Through the Subungual Space
November 2014 | Volume 13 | Issue 11 | Original Article | 1394 | Copyright © November 2014
Boni E. Elewski MD,a Richard A. Pollak, DPM MS,b Radhakrishnan Pillai PhD,c Jason T. Olin PhDd
aDepartment of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, AL
bSan Antonio Podiatry Associates, San Antonio, TX
cDow Pharmaceutical Sciences Inc. a Division of Valeant Pharmaceuticals North America, LLC., Bridgewater, NJ
dValeant Pharmaceuticals North America, LLC., Bridgewater, NJ
OBJECTIVE: To evaluate the ability of efinaconazole vehicle to reach the site of toenail onychomycosis by spreading through the subungual space between the nail plate and nail bed. Lacquer-based vehicles are primarily limited to application on the nail plate and dependent on nail plate permeation.
METHODS: 11 patients (mean age 48.5 years) were entered with clinically determined onychomycosis. Presence of fungal infection was confirmed by KOH testing in eight patients. Two separate applications of vehicle (with fluorescein incorporated for better visualization) were applied at the hyponychium, avoiding application to the exterior nail plate surface. Affected nails were later clipped to allow examination of the nail bed and further examination of the underside of the nail. Spread of formulation was assessed under visible and UV light conditions by photographing target toenails after vehicle application, and after nail clipping.
RESULTS: Assessments under both visible and UV light indicated that the vehicle had spread into the subungual space, with deposition of flourescein wherever vehicle had reached, including in the nail bed. Nail clippings also indicated deposition to the underside of the nail plate.
LIMITATIONS: The relative contributions of spreading into the subungual space, or permeation through the nail plate to the efficacy of efinaconazole topical solution, 10% in treating onychomycosis were not assessed.
CONCLUSIONS: This study suggests that the vehicle developed for efinaconazole topical solution, 10%, when applied at the hyponychium, spreads into the subungual space between the nail plate and nail bed, reaching the site of infection.
J Drugs Dermatol.
Onychomycosis is a difficult to treat fungal infection of the nails that results in nail discoloration, thickening and deformity.1,2 In distal and lateral subungual onychomycosis (DLSO), it is believed that the fungal infection starts as an extension of tinea pedis at the hyponychium and the distal or lateral nail bed. The fungus then invades the distal and lateral nail bed and ventral nail plate.3,4 Dermatophytes may be present in multiple sites adjacent to the toenail, including the nail bed, and the nailfolds. See Figure 1.
Topical onychomycosis therapy permits application of medication directly to the infected area, low potential for systemic drug exposure and low potential to cause systemic adverse events (AEs) or drug interactions. Yet, lacquer-based topical therapies are placed primarily on the exterior nail plate, depending upon the drug to reach the infection site mostly through nail permeation.5-7
Research over the last decade has focused on improving nail permeability by means of chemical treatment, penetration enhancers, mechanical and physical methods.
Efinaconazole topical solution, 10%, was developed with attention placed specifically on creating a vehicle with low surface tension and greater probability of nail plate permeation and access through the subungual space.8,9 Multiple vehicles were considered before arriving on the final formulation. 8 Delivery of efinaconazole topical solution, 10%, through the nail plate has been demonstrated in onychomycosis patients.9
Efinaconazole topical solution, 10%, has demonstrated its safety and efficacy in two well-controlled phase 3 trials, and is approved for treatment of DLSO in the United States and Canada.10 It has a broad spectrum of antifungal activity against the organisms most associated with toenail onychomycosis.11
Given that the product instructions state that the drug be applied to the clean, dry nail plate surface, lateral and proximal nailfolds, hyponychium, and undersurface of the nail plate,12 (Figure 1) we were interested in determining whether efinaconazole also reaches the infection site via capillary action through the subungual space that separates the nail plate from the nail bed.
This was a single center, 1-day study designed to evaluate the spreading efficiency of efinaconazole vehicle under the nail plate in male and female patients with toenail onychomycosis.