The Presence of an Air Gap Between the Nail Plate and Nail Bed in Onychomycosis Patients: Treatment Implications for Topical Therapy

August 2015 | Volume 14 | Issue 8 | Original Article | 859 | Copyright © 2015

Aditya K. Gupta MD PhD FRCPC FAADa,b and Radhakrishnan Pillai PhDc

aDepartment of Medicine, University of Toronto, Toronto, Canada
bMediprobe Research, London, Ontario, Canada
cDow Pharmaceutical Sciences Inc. (a division of Valeant Pharmaceuticals), Petaluma, CA

Abstract

BACKGROUND: Transungual nail penetrance has traditionally been considered to be the only route of delivery for topical antifungals in onychomycosis. Subungual penetrance may be an alternate route of delivery.
OBJECTIVE: To evaluate the ability of efinaconazole vehicle solution to reach the site of toenail onychomycosis through application to the hyponychium or hyponychium and dorsal nail surface, and assess the impact of the air gap between the nail plate and nail bed.
METHODS: Twenty-three participants with moderate to severe, mycologically-confirmed onychomycosis were enrolled (mean age, 48.5 years). Two separate applications of vehicle solution containing fluorescein for visualization were applied at the hyponychium or hyponychium and dorsal nail surface. Affected nails were later clipped to allow examination of the nail bed and further examination of the ventral surface 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: There was a positive correlation between the size of the air gap and degree of affected nail involvement (R2=0.064). Assessments under both visible and UV light indicated that the vehicle had spread to the site of infection, with deposition of fluorescein wherever vehicle had reached, irrespective of application methodology or size of air gap. Nail clippings also indicated absorption into the ventral surface of the nail plate.
LIMITATIONS: The relative contributions of subungual versus transungual application of drug to the nail plate to the efficacy of efinaconazole topical solution, 10% in treating onychomycosis were not assessed.
CONCLUSIONS: This study suggests that the low surface tension vehicle developed for efinaconazole topical solution, 10% can reach the site of infection by application to the hyponychium, dorsal or ventral nail surface and nail folds. This multidirectional approach to drug delivery at the site of fungal infection may contribute to the magnitude of efficacy seen in clinical trials.

J Drugs Dermatol. 2015;14(8):859-863.

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INTRODUCTION

Onychomycosis is a common fungal infection of the toenails or fingernails, representing around half of all nail diseases, and affecting 10%-20% of adults, particularly the elderly where the prevalence may be as high as 40% to 70%.1,2 Additionally, diabetics are three times more prone to onychomycosis when compared to age and sex-matched controls. 3 Older adults are also at increased risk of nail alterations; with secondary factors such as impaired circulation at the distal extremities, faulty biomechanics, infections and skin diseases affecting the nail plate or involving other components of the nail unit such as the matrix, nail bed, hyponychium, or nail folds.4

Onychomycosis may be treated with both oral and topical medication. Topical treatments reduce the risk of hepatotoxic side effects associated with some systemic antifungals but, traditional topical medication has provided relatively low cure rates and long treatment times (12 months or longer).2 One reason suggested for their low cure rates is the inability of active agent to penetrate the nail plate; however, the healthy nail unit is generally used to study penetration and there remains a need to conduct such studies in the presence of disease.5-7

There are substantial differences in healthy and onychomycotic nails that may alter drug penetration. Onychomycotic nails are thicker and slower growing. Healthy nails tend to have a thickness between 0.3-1.0mm, with toenail growth of 1.0mm per month.8 With advancing age, starting at the age of 25 years, this rate tends to decrease by approximately 0.5% per year.9,10 A comparative study of diseased and healthy nails showed that chronic nail plate infection increased nail thickness from 0.49±0.15mm (healthy) to 1.20±0.67mm (diseased, P<.05),11 confirming observations seen in clinical studies.12 Electron

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