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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.

Effects of Divalent Cations on Binding of Aminoglycoside Antibiotics to Human Serum Proteins and to Bacteria