Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization–Fourier Transform Ion Cyclotron Resonance Imaging
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 concentrat...
Ausführliche Beschreibung
Autor*in: |
Joly-Tonetti, Nicolas [verfasserIn] Legouffe, Raphael [verfasserIn] Tomezyk, Aurore [verfasserIn] Gumez, Clémence [verfasserIn] Gaudin, Mathieu [verfasserIn] Bonnel, David [verfasserIn] Schaller, Martin [verfasserIn] |
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E-Artikel |
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Englisch |
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2024 |
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Anmerkung: |
© The Author(s) 2024 |
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Übergeordnetes Werk: |
Enthalten in: Infectious diseases and therapy - Springer Healthcare, 2012, 13(2024), 6 vom: 07. Mai, Seite 1281-1290 |
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Übergeordnetes Werk: |
volume:13 ; year:2024 ; number:6 ; day:07 ; month:05 ; pages:1281-1290 |
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DOI / URN: |
10.1007/s40121-024-00979-2 |
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Katalog-ID: |
SPR055988644 |
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100 | 1 | |a Joly-Tonetti, Nicolas |e verfasserin |0 (orcid)0009-0008-8491-6978 |4 aut | |
245 | 1 | 0 | |a Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization–Fourier Transform Ion Cyclotron Resonance Imaging |
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520 | |a 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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650 | 4 | |a Infection |7 (dpeaa)DE-He213 | |
650 | 4 | |a MALDI-FTICR |7 (dpeaa)DE-He213 | |
650 | 4 | |a MALDI-MSI |7 (dpeaa)DE-He213 | |
650 | 4 | |a Nails |7 (dpeaa)DE-He213 | |
650 | 4 | |a Onychomycosis |7 (dpeaa)DE-He213 | |
650 | 4 | |a Terbinafine |7 (dpeaa)DE-He213 | |
700 | 1 | |a Legouffe, Raphael |e verfasserin |0 (orcid)0000-0002-2421-1385 |4 aut | |
700 | 1 | |a Tomezyk, Aurore |e verfasserin |4 aut | |
700 | 1 | |a Gumez, Clémence |e verfasserin |4 aut | |
700 | 1 | |a Gaudin, Mathieu |e verfasserin |0 (orcid)0009-0002-1607-0313 |4 aut | |
700 | 1 | |a Bonnel, David |e verfasserin |0 (orcid)0009-0004-4159-261X |4 aut | |
700 | 1 | |a Schaller, Martin |e verfasserin |0 (orcid)0000-0002-7930-1919 |4 aut | |
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10.1007/s40121-024-00979-2 doi (DE-627)SPR055988644 (SPR)s40121-024-00979-2-e DE-627 ger DE-627 rakwb eng 610 VZ Joly-Tonetti, Nicolas verfasserin (orcid)0009-0008-8491-6978 aut 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 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. Amorolfine (dpeaa)DE-He213 Infection (dpeaa)DE-He213 MALDI-FTICR (dpeaa)DE-He213 MALDI-MSI (dpeaa)DE-He213 Nails (dpeaa)DE-He213 Onychomycosis (dpeaa)DE-He213 Terbinafine (dpeaa)DE-He213 Legouffe, Raphael verfasserin (orcid)0000-0002-2421-1385 aut Tomezyk, Aurore verfasserin aut Gumez, Clémence verfasserin aut Gaudin, Mathieu verfasserin (orcid)0009-0002-1607-0313 aut Bonnel, David verfasserin (orcid)0009-0004-4159-261X aut Schaller, Martin verfasserin (orcid)0000-0002-7930-1919 aut Enthalten in Infectious diseases and therapy Springer Healthcare, 2012 13(2024), 6 vom: 07. Mai, Seite 1281-1290 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:13 year:2024 number:6 day:07 month:05 pages:1281-1290 https://dx.doi.org/10.1007/s40121-024-00979-2 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2024 6 07 05 1281-1290 |
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10.1007/s40121-024-00979-2 doi (DE-627)SPR055988644 (SPR)s40121-024-00979-2-e DE-627 ger DE-627 rakwb eng 610 VZ Joly-Tonetti, Nicolas verfasserin (orcid)0009-0008-8491-6978 aut 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 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. Amorolfine (dpeaa)DE-He213 Infection (dpeaa)DE-He213 MALDI-FTICR (dpeaa)DE-He213 MALDI-MSI (dpeaa)DE-He213 Nails (dpeaa)DE-He213 Onychomycosis (dpeaa)DE-He213 Terbinafine (dpeaa)DE-He213 Legouffe, Raphael verfasserin (orcid)0000-0002-2421-1385 aut Tomezyk, Aurore verfasserin aut Gumez, Clémence verfasserin aut Gaudin, Mathieu verfasserin (orcid)0009-0002-1607-0313 aut Bonnel, David verfasserin (orcid)0009-0004-4159-261X aut Schaller, Martin verfasserin (orcid)0000-0002-7930-1919 aut Enthalten in Infectious diseases and therapy Springer Healthcare, 2012 13(2024), 6 vom: 07. Mai, Seite 1281-1290 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:13 year:2024 number:6 day:07 month:05 pages:1281-1290 https://dx.doi.org/10.1007/s40121-024-00979-2 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2024 6 07 05 1281-1290 |
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10.1007/s40121-024-00979-2 doi (DE-627)SPR055988644 (SPR)s40121-024-00979-2-e DE-627 ger DE-627 rakwb eng 610 VZ Joly-Tonetti, Nicolas verfasserin (orcid)0009-0008-8491-6978 aut 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 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. Amorolfine (dpeaa)DE-He213 Infection (dpeaa)DE-He213 MALDI-FTICR (dpeaa)DE-He213 MALDI-MSI (dpeaa)DE-He213 Nails (dpeaa)DE-He213 Onychomycosis (dpeaa)DE-He213 Terbinafine (dpeaa)DE-He213 Legouffe, Raphael verfasserin (orcid)0000-0002-2421-1385 aut Tomezyk, Aurore verfasserin aut Gumez, Clémence verfasserin aut Gaudin, Mathieu verfasserin (orcid)0009-0002-1607-0313 aut Bonnel, David verfasserin (orcid)0009-0004-4159-261X aut Schaller, Martin verfasserin (orcid)0000-0002-7930-1919 aut Enthalten in Infectious diseases and therapy Springer Healthcare, 2012 13(2024), 6 vom: 07. Mai, Seite 1281-1290 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:13 year:2024 number:6 day:07 month:05 pages:1281-1290 https://dx.doi.org/10.1007/s40121-024-00979-2 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2024 6 07 05 1281-1290 |
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10.1007/s40121-024-00979-2 doi (DE-627)SPR055988644 (SPR)s40121-024-00979-2-e DE-627 ger DE-627 rakwb eng 610 VZ Joly-Tonetti, Nicolas verfasserin (orcid)0009-0008-8491-6978 aut 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 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. Amorolfine (dpeaa)DE-He213 Infection (dpeaa)DE-He213 MALDI-FTICR (dpeaa)DE-He213 MALDI-MSI (dpeaa)DE-He213 Nails (dpeaa)DE-He213 Onychomycosis (dpeaa)DE-He213 Terbinafine (dpeaa)DE-He213 Legouffe, Raphael verfasserin (orcid)0000-0002-2421-1385 aut Tomezyk, Aurore verfasserin aut Gumez, Clémence verfasserin aut Gaudin, Mathieu verfasserin (orcid)0009-0002-1607-0313 aut Bonnel, David verfasserin (orcid)0009-0004-4159-261X aut Schaller, Martin verfasserin (orcid)0000-0002-7930-1919 aut Enthalten in Infectious diseases and therapy Springer Healthcare, 2012 13(2024), 6 vom: 07. Mai, Seite 1281-1290 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:13 year:2024 number:6 day:07 month:05 pages:1281-1290 https://dx.doi.org/10.1007/s40121-024-00979-2 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2024 6 07 05 1281-1290 |
allfieldsSound |
10.1007/s40121-024-00979-2 doi (DE-627)SPR055988644 (SPR)s40121-024-00979-2-e DE-627 ger DE-627 rakwb eng 610 VZ Joly-Tonetti, Nicolas verfasserin (orcid)0009-0008-8491-6978 aut 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 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 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. Amorolfine (dpeaa)DE-He213 Infection (dpeaa)DE-He213 MALDI-FTICR (dpeaa)DE-He213 MALDI-MSI (dpeaa)DE-He213 Nails (dpeaa)DE-He213 Onychomycosis (dpeaa)DE-He213 Terbinafine (dpeaa)DE-He213 Legouffe, Raphael verfasserin (orcid)0000-0002-2421-1385 aut Tomezyk, Aurore verfasserin aut Gumez, Clémence verfasserin aut Gaudin, Mathieu verfasserin (orcid)0009-0002-1607-0313 aut Bonnel, David verfasserin (orcid)0009-0004-4159-261X aut Schaller, Martin verfasserin (orcid)0000-0002-7930-1919 aut Enthalten in Infectious diseases and therapy Springer Healthcare, 2012 13(2024), 6 vom: 07. Mai, Seite 1281-1290 (DE-627)735690766 (DE-600)2701611-0 2193-6382 nnns volume:13 year:2024 number:6 day:07 month:05 pages:1281-1290 https://dx.doi.org/10.1007/s40121-024-00979-2 X:SPRINGER Resolving-System kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 13 2024 6 07 05 1281-1290 |
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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. 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610 VZ Penetration Profile of Terbinafine Compared to Amorolfine in Mycotic Human Toenails Quantified by Matrix-Assisted Laser Desorption Ionization–Fourier Transform Ion Cyclotron Resonance Imaging Amorolfine (dpeaa)DE-He213 Infection (dpeaa)DE-He213 MALDI-FTICR (dpeaa)DE-He213 MALDI-MSI (dpeaa)DE-He213 Nails (dpeaa)DE-He213 Onychomycosis (dpeaa)DE-He213 Terbinafine (dpeaa)DE-He213 |
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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 |
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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 |
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Joly-Tonetti, Nicolas Legouffe, Raphael Tomezyk, Aurore Gumez, Clémence Gaudin, Mathieu Bonnel, David Schaller, Martin |
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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 |
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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 |
abstract |
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. © The Author(s) 2024 |
abstractGer |
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. © The Author(s) 2024 |
abstract_unstemmed |
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. © The Author(s) 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 |
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