ATTENUATION BY DAPTOMYCIN OF GENTAMICIN-INDUCED EXPERIMENTAL NEPHROTOXICITY

Female Sprague-Dawley rats were treated with saline (NaCl, 0.9%), dapt omycin (10 mg/kg of body weight every 12 h, subcutaneously), gentamici n (30 mg/kg/12 h, intraperitoneally) or with a combination of daptomyc in plus gentamicin over a 10-day period. Animals were killed 4, 10, an d 20 days after the end of treatment. Four days after the end of drug administration, gentamicin and daptomycin levels in the renal cortices of animals treated with the combination of daptomycin and gentamicin were significantly higher than in those of rats given gentamicin or da ptomycin alone (P < 0.01). Despite the higher cortical concentrations of gentamicin, rats given the combination of gentamicin and daptomycin had less reduction in renal cortex sphingomyelinase activity, less ev idence of regeneration of cellular cortical cells ([H-3]thymidine inco rporation into cortex DNA), lower creatinine concentration in serum, a nd less histopathologic evidence of injury than rats given gentamicin alone. By immunogold technique, both daptomycin and gentamicin were lo calized to the lysosomes of proximal tubular cells, regardless of whet her animals received the drugs alone or in combination. Interestingly, myeloid body formation occurred in both those animals given gentamici n alone and those given daptomycin plus gentamicin. No significant cha nges were observed for all groups between 10 and 20 days after the end of therapy, suggesting that the toxicity of gentamicin was not delaye d by the concomitant injection of daptomycin. The results confirm that daptomycin can attenuate experimental gentamicin nephrotoxicity.