Nephrotoxicity of teicoplanin in rats

Teicoplanin, a glycopeptide antibiotic, is marketed in a number of European countries and has recently been put on the market in Japan. The spectrum of antibacterial activity of teicoplanin is equivalent or superior to that of vancomycin. The aim of the present study is to examine the nephrotoxicity of teicoplanin compared with vancomycin in rats. Wistar male rats, housed in a light-controlled room at room temperature for 1 week, were used. They were injected with either 15 or 50 mg/kg/day of teicoplanin or 50 or 200 mg/kg/day of vancomycin at 13:00 daily for 14 days. The rats were randomly assigned to groups of five rats each and were housed individually in metabolic cages to collect urine. Urine samples were collected 24 hours prior to the drug treatment and every 24 hours thereafter for 14 days. N-Acetyl-beta-D-glucosaminidase (NAG) activity was determined in the supernatant and expressed in international units per total urine collected for 24 hours. The group which was given vancomycin 200 mg/kg/day had significantly elevated urinary NAG levels compared with the other groups (p < 0.05). No significant differences were observed in the NAG levels in urine among the remaining three groups. These results suggest that the nephrotoxicity of teicoplanin may be only one-fourth that of vancomycin in rats. It appears that by extrapolating the dose amount required for the treatment in humans to rats, the high dose of teicoplanin was set at 50 mg/kg/day and that of vancomycin, 200 mg/kg/day. The recommended dose for teicoplanin will probably be 200 mg/day compared to 2 g/day of vancomycin. If the teicoplanin dose is only one-tenth that of the vancomycin dose, then teicoplanin should be better tolerated than vancomycin in terms of nephrotoxicity.