Toxicology of vancomycin in laboratory animals

The 50% lethal dose (LD50) of vancomycin for rodents was higher than that of tobramycin but much lower than that of cefamandole nafate. The rodents died in clonic convulsions immediately after receiving vancomycin. The LD50 for dogs similar to that for rodents; however, deaths occurred several days after administration of vancomycin and resulted from renal failure. Rapid intravenous administration of vancomycin to dogs produced a significant decrease in blood pressure that was prevented by pretreatment with the antihistamine methapyrilene. Subchronic administration of vancomycin to laboratory animals in doses of 12.5-400 mg/kg caused no systemic toxicity. Concomitant administration of vancomycin and tobramycin to rats resulted in significantly increased nephrotoxicity compared to that caused by either agent alone. The nephrotoxic response of rats receiving vancomycin was only partially reversed by large volumes of water given orally before and after the drug.