Renal tolerance and pharmacokinetics of vancomycin in rats.

The nephrotoxicity, as measured by urinary cell and enzyme excretion, of vancomycin was studied in rats. The lowest daily iv dose inducing significantly increased cell elimination was 25 mg/kg. Im administration caused less effects probably due to incomplete absorption from the im injection site, since im dosages of 100 mg/kg daily led to lower renal tissue concentrations than the same doses given iv. Nephrotoxicity of vancomycin increased when combined with tobramycin and was reduced when combined with D-glucaro-1.5-lactam, a beta-glucuronidase inhibitor. Vancomycin accumulated in renal tissue during repeated administration.