Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (6): A mechanism for the suppressive action of latamoxef on intrarenal tobramycin level.

The mechanism by which latamoxef (LMOX) reduces intrarenal tobramycin (TOB) levels was studied. When TOB (90 mg/kg/day, s.c.) and LMOX (500 or 2000 mg/kg/day, s.c.) were given simultaneously at separate sites to rats, 20 to 30% reductions in intrarenal TOB concentration were found on the 1st and 3rd days, as compared with the results from using TOB alone. The treatment with the reaction mixture of TOB and LMOX, which was preincubated for 3 hr at 37 degrees C to form the complex of TOB and LMOX, resulted in a greater suppression of TOB level in the kidney than administration of TOB and LMOX concomitantly at separate sites. When LMOX was given to rats 0.5 or 1.5 hr before s.c. injection of TOB, there were significant reductions in intrarenal TOB concentration. However, treatment with LMOX 5 hr before, as well as 1.5 or 5 hr after TOB injection, was ineffective in reducing the accumulation of TOB in the kidney. In the rats given both drugs simultaneously, the urinary excretion pattern of TOB almost overlapped with that of LMOX. Additionally, we detected a complex of TOB and LMOX in the urine of rats given both drugs simultaneously. These results suggest that the suppressive action of LMOX on intrarenal TOB level is due to the interaction of TOB and LMOX.