Aminoglycoside Antibiotics: Chemistry

Aminoglycoside Antibiotics

CHEMISTRY

Aminoglycosides are hydrophilic, polycationic, amine-containing carbohydrates that are usually composed of three to five rings. Most aminoglycosides are either nat-ural products or derivatives of soil actinomycetes. They are often secreted by these actinomycetes as mixtures of closely related compounds. The polycationic amino-glycoside chemical structure results in a binding both to the anionic outer bacterial membrane and to anionic phospholipids in the cell membranes of mammalian re-nal proximal tubular cells. The former contributes to the bactericidal effects of these compounds, while the latter binding accounts for their toxicity. Because of their hy-drophilicity, the transport of aminoglycosides across the hydrophobic lipid bilayer of eukaryotic cell membranes is impeded.

The major clinically important aminoglycosides are amikacin (Amikin), gentamicin (Garamycin), kanamycin (Kantrex), netilmicin (Netromycin), neomycin (Myci-fradin), streptomycin, and tobramycin (Nebcin). Their pharmacokinetic characteristics are shown in Table 46.1.