[Effect of keratin on the efficacy of fluconazole].
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 keratin and azole derivatives.
Klimke
K
K
Abteilung für Pharmakologie und Toxikologie, Freie Universität Berlin, BR Deutschland.
Schäfer-Korting
M
M
D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D015725:Fluconazole / Q000493:pharmacokinetics* / Q000494:pharmacology; D017964:Itraconazole / Q000493:pharmacokinetics; D007633:Keratins / Q000493:pharmacokinetics / Q000494:pharmacology*; D007654:Ketoconazole / Q000493:pharmacokinetics; D007700:Kinetics; D012756:Sheep; D012867:Skin / Q000378:metabolism; D014935:Wool
D000935:Antifungal Agents; D001798:Blood Proteins; D017964:Itraconazole; D007633:Keratins; D015725:Fluconazole; D007654:Ketoconazole