title: Post-antibiotic effect and post-expositional polyene antagonism of azole antifungal agents in Candida albicans: dependence on substance lipophilia.
abstract: The lipophilic azoles itraconazole (ICZ), ketoconazole (KCZ) and miconazole (MCZ) have two things in common regarding their effect on Candida albicans. First, these azoles cause a growth inhibition that persists for at least 24 h after exposure (post-antibiotic effect), although this is only occasionally observed for ICZ. Secondly, these substances cause a decrease in the fungicidal activity of amphotericin B (AMB, 1 mg l-1) upon subsequent exposure to this drug. In contrast, fluconazole (FCZ) exhibits neither of these two effects. Further tests suggest that both of these phenomena observed may be related to the non-covalent binding of the three lipophilic azoles to lipophilic cytoplasmic components of yeast cells. With fluconazole, such bonds seem to be much weaker. The amount of relatively hydrophilic fluconazole that is bound non-specifically to the fungal cell is evidently too low to produce long-lasting post-exposure effects like those caused by lipophilic azoles.
authors.affiliation: Medicinal, Food and Veterinary Investigational Authority Thüringen, Gera, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Scheven
authors.forename: C
authors.initials: C
authors.lastname: Scheven
authors.forename: K
authors.initials: K
authors.lastname: Hahn
authors.forename: A
authors.initials: A
authors.lastname: Senf
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001393:Azoles / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000254:growth & development; D004347:Drug Interactions; D015725:Fluconazole / Q000494:pharmacology; D017964:Itraconazole / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D017964:Itraconazole; D008825:Miconazole; D000666:Amphotericin B; D015725:Fluconazole; D007654:Ketoconazole