Ramirez-Ronda C H, Holmes R K, Sanford J P
Antimicrob Agents Chemother. 1975 Mar;7(3):239-45. doi: 10.1128/AAC.7.3.239.
Binding of gentamicin and related deoxystreptamine-containing aminoglycoside antibiotics to proteins in human serum can vary significantly with changes in experimental conditions. The concentrations of divalent cations are important variables, and binding increases progressively as the concentrations of calcium and magnesium decrease. Maximal binding of deoxystreptamine-containing aminoglycosides to human serum is approximately 70% in the absence of divalent cations. The binding of (3)H-labeled gentamicin to Pseudomonas aeruginosa increases and its bactericidal activity against P. aeruginosa is enhanced in the absence of divalent cations. In contrast, binding of (3)H-labeled gentamicin to Escherichia coli and bactericidal activity against E. coli do not vary significantly in the presence and in the absence of divalent cations. Interference with uptake of gentamicin provides a plausible explanation for the observation that the minimal inhibitory concentration of gentamicin for P. aeruginosa increases as the concentration of calcium or magnesium in bacteriological media increases. Although significant binding of deoxystreptamine-containing aminoglycosides to plasma proteins does not occur under normal physiological conditions in man, the possibility remains that variations in protein binding of these aminoglycosides might be significant under pathological conditions.
庆大霉素及相关含脱氧链霉胺氨基糖苷类抗生素与人血清中蛋白质的结合会因实验条件的改变而有显著差异。二价阳离子浓度是重要变量，随着钙和镁浓度降低，结合作用逐渐增强。在无二价阳离子的情况下，含脱氧链霉胺氨基糖苷类抗生素与人血清的最大结合率约为70%。在无二价阳离子时，（3）H标记的庆大霉素与铜绿假单胞菌的结合增加，且其对铜绿假单胞菌的杀菌活性增强。相比之下，（3）H标记的庆大霉素与大肠杆菌的结合以及对大肠杆菌的杀菌活性在有或无二价阳离子时并无显著差异。对庆大霉素摄取的干扰为以下观察结果提供了一个合理的解释：随着细菌培养基中钙或镁浓度增加，庆大霉素对铜绿假单胞菌的最低抑菌浓度升高。虽然在正常生理条件下，含脱氧链霉胺氨基糖苷类抗生素与血浆蛋白不会发生显著结合，但在病理条件下，这些氨基糖苷类抗生素的蛋白结合变化仍有可能具有重要意义。
