PMID: 9417512Jan 1, 1997Paper

Effect of keratin on the efficacy of fluconazole

Mycoses
K Klimke, M Schäfer-Korting

Abstract

In this study we have investigated the influence of keratin on the efficacy and pharmacokinetics of fluconazole and additional azole antifungal agents. It is well known that the penetration and distribution of oral antifungals is strongly influenced by plasma protein binding. Especially, itraconazole and ketoconazole show a high binding affinity to plasma proteins, whereas fluconazole binds only with 12%. All of these antifungals, however, are accumulated in the stratum corneum of the skin. These observations have stimulated interest, if structure proteins of the skin like keratin interact with antifungals may explain of the accumulation process. Therefore we have measured the binding kinetics between keratin and the azoles. Keratin from sheep wool was degreased, purified and incubated with azole antifungals. After defined incubation periods the azoles were extracted and assayed by thin layer chromatography following UV-detection. There was a specific binding between keratin and all of the used substances. Interestingly, the binding affinity of fluconazole to keratin was much higher than to plasma proteins. Thus our observations indicate that the accumulation in the stratum corneum is a consequence of the interaction between ke...Continue Reading

References

Oct 1, 1991·Antimicrobial Agents and Chemotherapy·M Schäfer-KortingA Lukacs
Feb 1, 1988·Journal of the American Academy of Dermatology·G CauwenberghK Haeverans
Dec 1, 1983·Antimicrobial Agents and Chemotherapy·R HarrisW M Artis
Sep 1, 1995·Infection·M Schäfer-KortingW Obermüller

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Citations

Apr 25, 2007·Drug Development and Industrial Pharmacy·Alessandra C AyubLucas A M Ferreira
Oct 22, 2010·Expert Opinion on Drug Delivery·Indu Pal Kaur, Shilpa Kakkar

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