Serum fungistatic and fungicidal activity in volunteers receiving antifungal agents

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Abstract
The serum levels of two imidazoles, ketoconazole and Bayer n7133, when administered alone or in combination with rifampin, were measured in volunteers and the serum antifungal activity was determined against various fungal strains. Serum levels were measured by high pressure liquid chromatography and correlated with serum fungistatic activity as determined in microtiter plates. Ketoconazole showed a wide range of serum levels, suggesting individual variations. The addition of two doses of rifampin significantly decreased serum levels of both imidazoles and no synergism was observed. Serum fungicidal activity could only occasionally be demonstrated against one strain of Candida albicans and Candida stellatoidea.Serum fungistatic activity significantly correlated with the serum levels of both imidazoles. This approach should be investigated in patients to establish its potential clinical relevance for managing invasive fungal infections.