Determinants of the in vitro interaction of polyaspartic acid and aminoglycoside antibiotics.
The in vitro interaction of polyaspartic acid (PAA) with aminoglycosides was evaluated using double diffusion in agar, dialysis chambers and changes in the optical density of test solutions. The results document a reversible, presumably electrostatic interaction that is optimized at a pH of approximately 5.0, by the absence of proteins over 800 Da, and at a 20:1 or 10:1 molar ratio of aminoglycoside to PAA. The PAA-aminoglycoside complex lost antibacterial activity and the ability to inhibit pronase E enzymatic activity. These results allow generation of a hypothesis as to the mechanism whereby PAA prevents aminoglycoside experimental nephrotoxicity.
Kohlhepp
S J
SJ
Infectious Diseases Research Laboratory, Chiles Research Institute, Providence Medical Center, Portland, Oregon.
McGregor
D N
DN
Cohen
S J
SJ
Kohlhepp
M E
ME
Gilbert
D N
DN
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000633:toxicity; D001790:Blood Physiological Phenomena; D004347:Drug Interactions; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D010455:Peptides; C017645:polyaspartate