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Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization–Fourier Transform Ion Cyclotron Resonance Imaging
by
Tomezyk, Aurore
, Joly-Tonetti, Nicolas
, Legouffe, Raphael
, Schaller, Martin
, Bonnel, David
, Gaudin, Mathieu
, Gumez, Clémence
in
Amorolfine
/ Analysis
/ Antifungal agents
/ Desorption
/ Diagnosis
/ Dosage and administration
/ Drug therapy
/ Fourier transforms
/ Infection
/ Infectious Diseases
/ Internal Medicine
/ Ionization
/ Keratin
/ MALDI-FTICR
/ MALDI-MSI
/ Mass spectrometry
/ Medicine
/ Medicine & Public Health
/ Methods
/ Nails
/ Onychomycosis
/ Original Research
/ Patient outcomes
/ Resonance
/ Terbinafine
2024
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Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization–Fourier Transform Ion Cyclotron Resonance Imaging
by
Tomezyk, Aurore
, Joly-Tonetti, Nicolas
, Legouffe, Raphael
, Schaller, Martin
, Bonnel, David
, Gaudin, Mathieu
, Gumez, Clémence
in
Amorolfine
/ Analysis
/ Antifungal agents
/ Desorption
/ Diagnosis
/ Dosage and administration
/ Drug therapy
/ Fourier transforms
/ Infection
/ Infectious Diseases
/ Internal Medicine
/ Ionization
/ Keratin
/ MALDI-FTICR
/ MALDI-MSI
/ Mass spectrometry
/ Medicine
/ Medicine & Public Health
/ Methods
/ Nails
/ Onychomycosis
/ Original Research
/ Patient outcomes
/ Resonance
/ Terbinafine
2024
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Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization–Fourier Transform Ion Cyclotron Resonance Imaging
by
Tomezyk, Aurore
, Joly-Tonetti, Nicolas
, Legouffe, Raphael
, Schaller, Martin
, Bonnel, David
, Gaudin, Mathieu
, Gumez, Clémence
in
Amorolfine
/ Analysis
/ Antifungal agents
/ Desorption
/ Diagnosis
/ Dosage and administration
/ Drug therapy
/ Fourier transforms
/ Infection
/ Infectious Diseases
/ Internal Medicine
/ Ionization
/ Keratin
/ MALDI-FTICR
/ MALDI-MSI
/ Mass spectrometry
/ Medicine
/ Medicine & Public Health
/ Methods
/ Nails
/ Onychomycosis
/ Original Research
/ Patient outcomes
/ Resonance
/ Terbinafine
2024
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Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization–Fourier Transform Ion Cyclotron Resonance Imaging
Journal Article
Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization–Fourier Transform Ion Cyclotron Resonance Imaging
2024
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Overview
Introduction
Amorolfine 5% lacquer is an established topical treatment for fungal infection of the nails. The success of topical therapy for onychomycosis depends on whether the permeated drug concentration in the deep nail bed is retained above the effective antifungal minimum inhibitory concentration (MIC). We compared the penetration profile of amorolfine and a new topical formula of terbinafine in human mycotic toenails using matrix-assisted laser desorption ionization mass spectrometry imaging–Fourier transform ion cyclotron resonance (MALDI-FTICR) imaging.
Methods
Amorolfine 5% lacquer and terbinafine 7.8% lacquer were applied to mycotic nails (
n
= 17); nail sections were prepared, and MALDI-FTICR analysis was performed. Based on the MICs of amorolfine and terbinafine needed to kill 90% (MIC
90
) of
Trichophyton rubrum
, the fold differences between the MIC
90
and the antifungal concentrations in the nails (the multiplicity of the MIC
90
) were calculated overall and for the keratin-unbound fractions.
Results
Both amorolfine and terbinafine penetrated the entire thickness of the nail. The mean concentration across the entire nail section 3 h following terbinafine treatment was 1414 μg/g of tissue (equivalent to 4.9 mM) compared with 780 μg/g (2.5 mM) following amorolfine treatment (not significantly different;
p
= 0.878). The median multiplicity of the MIC
90
was significantly higher in amorolfine- than terbinafine-treated nails overall (191 vs. 48;
p
= 0.010) and for the keratin-unbound fractions only (7.4 vs. 0.8;
p
= 0.002).
Conclusion
In this ex vivo study, MALDI-FTICR demonstrated that, although amorolfine 5% and terbinafine 7.8% had similar distribution profiles, both penetrating from the surface to the nail bed, the concentration of amorolfine in the nail was significantly higher than that of terbinafine relative to their respective MIC
90
values. Clinical studies are required to determine whether these effects translate to a clinical difference in treatment success.
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