EFFECTS OF FOSFOMYCIN AND IMIPENEM CILASTATIN ON NEPHROTOXICITY AND RENAL EXCRETION OF VANCOMYCIN IN RATS/

Purpose. The effects of fosfomycin and imipenem/cilastatin on the neph rotoxicity of vancomycin were studied in rats, and those on the renal handling of vancomycin were also investigated in perfused kidneys. Met hods. The protective effects of fosfomycin and imipenem/cilastatin on vancomycin nephrotoxicity were evaluated by increases in plasma concen tration of creatinine and urea nitrogen in rats. The urinary excretion of vancomycin was measured and analyzed kinetically in the perfused r at kidney. Results. The nephrotoxicity induced by vancomycin (500 mg/k g, i.v.) was inhibited almost completely by co-administration of fosfo mycin or imipenem/cilastatin. In the perfused rat kidney, the excretio n ratio of vancomycin was less than those of p-aminohippurate and cime tidine, and greater than that of arbekacin, suggesting the secretion a nd reabsorption of vancomycin in renal tubules. The tissue/perfusate r atios of unbound vancomycin were not significantly changed by co-treat rnent with fosfomycin or imipenem/cilastatin. Imipenem/cilastatin sign ificantly decreased the excretion ratio of vancomycin. Fosfomycin also decreased vancomycin excretion ratio, although this effect was not si gnificant. Conclusions. The renal handling of vancomycin was different from those of organic anions and cations and an aminoglycoside antibi otic. The protective effects of fosfomycin and imipenem/cilastatin aga inst the nephrotoxicity of vancomycin might be partly due to the chang e in renal handling of vancomycin, probably in its tubular secretion/r eabsorption, in rats.