• 1

    Scher RK. Advances in the diagnosis and treatment of onychomycosis. Hosp Med 34: 11, 1998.

  • 2

    Martinez E. Ameen M. Tejada D. et al: Microsporum spp. onychomycosis: disease presentation, risk factors and treatment responses in an urban population. Braz J Infect Dis 18: 181, 2014.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Alley MRK. Baker SJ. Beutner KR. et al: Recent progress on the topical therapy of onychomycosis. Exp Opin Invest Drugs 16: 157, 2007.

  • 4

    Thomas J. Jacobson GA. Narkowicz CK. et al: Toenail onychomycosis: an important global disease burden. J Clin Pharm Ther 35: 497, 2010.

  • 5

    Yaemsiri S. Hou N. Slining MM. et al: Growth rate of human fingernails and toenails in healthy American young adults. J Eur Acad Dermatol Venereol 24: 420, 2010.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Yu HJ. Kwon HM. Oh DH. et al: Is slow nail growth a risk factor for onychomycosis? Clin Exp Dermatol 29: 415, 2004.

  • 7

    Scher RK. Onychomycosis: a significant medical disorder. J Am Acad Dermatol 35: S2, 1996.

  • 8

    Ghannoum MA. Hajjeh RA. Scher R. et al: A large-scale North American study of fungal isolates from nails: the frequency of onychomycosis, fungal distribution, and antifungal susceptibility patterns. J Am Acad Dermatol 43: 641, 2000.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Prevalence, morbidity, and cost of dermatological diseases. J Invest Dermatol 73: 395, 1979.

  • 10

    Elewski BE. Charif MA. Prevalence of onychomycosis in patients attending a dermatology clinic in northeastern Ohio for other conditions. Arch Dermatol 133: 1172, 1997.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Elewski BE. Onychomycosis: pathogenesis, diagnosis, and management. Clin Microbiol Rev 11: 415, 1998.

  • 12

    Elewski BE. Aly R. Baldwin SL. et al: Efficacy and safety of tavaborole topical solution, 5%, a novel boron-based antifungal agent, for the treatment of toenail onychomycosis: results from 2 randomized phase-III studies. J Am Acad Dermatol 73: 62, 2015.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Barak O. Loo DS. AN-2690, a novel antifungal for the topical treatment of onychomycosis. Curr Opin Investig Drugs 8: 662, 2007.

  • 14

    Baker SJ. Ding CZ. Akama T. et al: Therapeutic potential of boron-containing compounds. Future Med Chem 1: 1275, 2009.

  • 15

    Del Rosso JQ. Plattner JJ. From the test tube to the treatment room: fundamentals of boron-containing compounds and their relevance to dermatology. J Clin Aesthet Dermatol 7: 13, 2014.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Hunter P. Not boring at all: boron is the new carbon in the quest for novel drug candidates. EMBO Rep 10: 125, 2009.

  • 17

    Baker SJ. Zhang YK. Akama T. et al: Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (AN2690), for the potential treatment of onychomycosis. J Med Chem 49: 4447, 2006.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    O'Dwyer K. Spivak AT. Ingraham K. et al: Bacterial resistance to leucyl-tRNA synthetase inhibitor GSK2251052 develops during treatment of complicated urinary tract infections. Antimicrob Agents Chemother 59: 289, 2015.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Rock FL. Mao W. Yaremchuk A. et al: An antifungal agent inhibits an aminoacyl-tRNA synthetase by trapping tRNA in the editing site. Science 316: 1759, 2007.

  • 20

    Coronado D. Merchant T. Chanda S. et al: In vitro nail penetration and antifungal activity of tavaborole, a boron-based pharmaceutical. J Drugs Dermatol 14: 609, 2015.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Hui X. Baker SJ. Wester RC. et al: In vitro penetration of a novel oxaborole antifungal (AN2690) into the human nail plate. J Pharm Sci 96: 2622, 2007.

  • 22

    Vlahovic T. MPharm TM. Chanda S. et al: In vitro nail penetration of tavaborole topical solution, 5%, through nail polish on ex vivo human fingernails. J Drugs Dermatol 14: 675, 2015.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Hold K. Bullington R. Jones T. et al: In vivo nail residence time of AN2690, a novel broad-spectrum antifungal agent in development for the topical treatment of onychomycosis [abstract]. J Am Acad Dermatol 56: AB128, 2007.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Hold KM. Sanders V. Bu W. et al: Nail penetration and nail concentration of AN2690, a novel broad-spectrum antifungal agent in development for the topical treatment of onychomycosis . Poster presented at: 2006 AAPS Annual Meeting and Exposition, October 29–November 2, 2006, San Antonio, TX.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Toledo-Bahena ME. Bucko A. Ocampo-Candiani J. et al: The efficacy and safety of tavaborole, a novel, boron-based pharmaceutical agent: phase 2 studies conducted for the topical treatment of toenail onychomycosis. J Drugs Dermatol 13: 1124, 2014.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Roberts DT. Taylor WD. Boyle J. Guidelines for treatment of onychomycosis. Br J Dermatol 148: 402, 2003.

  • 27

    Kerydin [package insert], PharmaDerm, a Division of Fougera Pharmaceuticals Inc, Melville, NY, 2015.

  • 28

    Ghannoum M. Isham N. Fungal nail infections (onychomycosis): a never-ending story? PLoS Pathog 10: e1004105, 2014.

  • 29

    Del Rosso JQ. The role of topical antifungal therapy for onychomycosis and the emergence of newer agents. J Clin Aesthet Dermatol 7: 10, 2014.

  • 30

    Barot BS. Parejiya PB. Patel HK. et al: Drug delivery to the nail: therapeutic options and challenges for onychomycosis. Crit Rev Ther Drug Carrier Syst 31: 459, 2014.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Murdan S. Poojary C. Patel DR. et al: In vivo measurement of the surface energy of human fingernail plates. Int J Cosmet Sci 34: 257, 2012.

  • 32

    Kobayashi Y. Miyamoto M. Sugibayashi K. et al: Drug permeation through the three layers of the human nail plate. J Pharm Pharmacol 51: 271, 1999.

  • 33

    Mertin D. Lippold BC. In-vitro permeability of the human nail and of a keratin membrane from bovine hooves: prediction of the penetration rate of antimycotics through the nail plate and their efficacy. J Pharm Pharmacol 49: 866, 1997.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Baden HP. Goldsmith LA. Fleming B. A comparative study of the physicochemical properties of human keratinized tissues. Biochim Biophys Acta 322: 269, 1973.

  • 35

    Schaefer UF. Hansen S. Schneider M. et al: “Models for Skin Absorption and Skin Toxicity Testing,” in Drug Absorption Studies: In Situ, In Vitro and In Silico Models, edited by E Carsten, KJ Kim, p 3, Springer Science & Business Media, New York, 2007.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Vejnovic I. Simmler L. Betz G. Investigation of different formulations for drug delivery through the nail plate. Int J Pharm 386: 185, 2010.

  • 37

    Elsayed MM. Development of topical therapeutics for management of onychomycosis and other nail disorders: a pharmaceutical perspective. J Control Release 199: 132, 2015.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation

Examining the Benefits of the Boron-Based Mechanism of Action and Physicochemical Properties of Tavaborole in the Treatment of Onychomycosis

Bryan Markinson Icahn School of Medicine at Mount Sinai, New York, NY.

Search for other papers by Bryan Markinson in
Current site
Google Scholar
PubMed
Close
 DPM
,
Mahmoud Ghannoum Department of Dermatology, Case Western Reserve University, Cleveland, OH.

Search for other papers by Mahmoud Ghannoum in
Current site
Google Scholar
PubMed
Close
 PhD, EMBA
,
Tate Winter Sandoz, a Novartis division, Princeton, NJ.

Search for other papers by Tate Winter in
Current site
Google Scholar
PubMed
Close
 PhD
,
Anthony Rycerz Sandoz, a Novartis division, Princeton, NJ.

Search for other papers by Anthony Rycerz in
Current site
Google Scholar
PubMed
Close
 PhD
,
Fernando Rock Anacor Pharmaceuticals Inc, a wholly owned subsidiary of Pfizer, Inc, New York, NY.

Search for other papers by Fernando Rock in
Current site
Google Scholar
PubMed
Close
 PhD
, and
Aditya K. Gupta Mediprobe Research Inc, London, Ontario, Canada.

Search for other papers by Aditya K. Gupta in
Current site
Google Scholar
PubMed
Close
 MD, PhD, FRCP(C)

Onychomycosis is a fungal infection of the nail primarily caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes. The topical-based treatment of onychomycosis remains a challenge because of the difficulty associated with penetrating the dense, protective structure of the keratinized nail plate. Tavaborole is a novel small-molecule antifungal agent recently approved in the United States for the topical treatment of toenail onychomycosis. The low molecular weight, slight water solubility, and boron chemistry of tavaborole maximize nail penetration after topical application, allowing for effective targeting of the infection in the nail bed. The efficacy of tavaborole is associated with its novel mechanism of action, whereby it inhibits the fungal leucyl-tRNA synthetase (LeuRS) enzyme. Because LeuRS is an essential component in fungal protein synthesis, inhibition of LeuRS ultimately leads to fungal cell death. Tavaborole is the first boron-based antifungal medication approved for the treatment of mild-to-moderate onychomycosis and presents patients with a new topical option. Previously, ciclopirox and efinaconazole were the only approved topical treatments for onychomycosis. This article details the properties that are at the core of the clinical benefits associated with tavaborole.

Corresponding author: Bryan Markinson, DPM, Icahn School of Medicine at Mount Sinai, 17 E 102nd St, New York, NY 10029. (E-mail: bryprof@aol.com)
Save