Uno J, Shigematsu M L, Arai T
Antimicrob Agents Chemother. 1983 Oct;24(4):552-9. doi: 10.1128/AAC.24.4.552.
Copiamycin, a macrocyclic lactone antifungal antibiotic, was found to potentiate the antifungal effect of imidazole compounds, ketoconazole in particular. The potentiation of two nominally fungistatic agents in vitro was substantiated by a marked reduction of the minimum inhibitory and minimum fungicidal concentrations when the drugs were used in combination. The effectiveness of this synergistic combination was also demonstrated in experimental murine candidosis. Evidence is presented to suggest that this combined effect is due, at least in part, to the ionophoretic property of copiamycin. Whereas amphotericin B induces a marked increase in cellular permeability, this antibiotic does not possess the ionophoretic action of copiamycin, indicating that the enhancement of copiamycin activity and significant reduction of amphotericin B activity by ketoconazole pretreatment can be ascribed not only to changes in membrane permeability of the test organisms, but also to the different action mechanisms of copiamycin and amphotericin B. It is thus plausible that the strong synergism of copiamycin with imidazole compounds is related to the ionophoretic activity of the antibiotic. Further studies on the biochemical mechanism of this synergistic effect are being conducted together with an assessment of the clinical significance of this drug combination.
发现大环内酯类抗真菌抗生素可匹霉素能增强咪唑类化合物（尤其是酮康唑）的抗真菌作用。当两种名义上的抑菌剂联合使用时，最低抑菌浓度和最低杀菌浓度显著降低，从而证实了它们在体外的增效作用。这种协同组合的有效性在实验性小鼠念珠菌病中也得到了证实。有证据表明，这种联合效应至少部分归因于可匹霉素的离子载体特性。两性霉素B可显著增加细胞通透性，而这种抗生素不具备可匹霉素的离子载体作用，这表明酮康唑预处理增强可匹霉素活性并显著降低两性霉素B活性，不仅可归因于受试生物体膜通透性的变化，还可归因于可匹霉素和两性霉素B不同的作用机制。因此，可匹霉素与咪唑类化合物的强协同作用可能与该抗生素的离子载体活性有关。目前正在对这种协同效应的生化机制进行进一步研究，并评估这种药物组合的临床意义。
