Effect of glucarolactam on ototoxicity of aminoglycoside antibiotics in guinea-pigs.
Intramuscular administration of glucarolactam in the form of aminoglycoside salt to guinea-pigs protected the experimental ototoxicity caused by high dosing of aminoglycoside antibiotics. The protection was evidenced by the pinna reflex threshold and histochemical examinations of hair cells of cochlea as well as body weight gain. The degree of protection differed with the aminoglycosides, and high protection was observed for dibekacin, gentamicin, tobramycin, followed by kanamycin and bekanamycin. However, protection was weak or not observed when glucarolactam was administered as a mixture of glucarolactam potassium and aminoglycoside sulfate. Serum analysis of the guinea-pigs on day 14 post-administration as a measure of nephrotoxicity revealed that glucarolactam suppressed the elevation of BUN and serum creatinine caused by the aminoglycosides. The protective effect of glucarolactam on the aminoglycoside-induced nephrotoxicity in the dehydrated rats did not differ between the salt and the mixture. No difference in the in vivo antibiotic activity against bacterial infections of mice was observed between the salt and the mixture.
Yokota
M
M
Central Research Laboratories, Meiji Seika Kaisha Ltd., Yokohama, Japan.
Niizato
T
T
Inouye
S
S
Kitasato
I
I
D000617:Aminoglycosides; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use / Q000633:toxicity*; D003051:Cochlea / Q000201:enzymology / Q000473:pathology; D003681:Dehydration / Q000503:physiopathology; D005937:Glucaric Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D006168:Guinea Pigs; D006311:Hearing Disorders / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011552:Pseudomonas Infections / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013400:Sugar Acids / Q000494:pharmacology*
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D013400:Sugar Acids; C001845:D-glucaro-delta-lactam; D013385:Succinate Dehydrogenase; D005937:Glucaric Acid