COMPARATIVE NEPHROTOXICITY OF LATAMOXEF AND OTHER CEPHALOSPORINS IN RABBITS

COMBINED ADMINISTRATION WITH FUROSEMIDE OF TOBRAMYCIN

Abstract

I. The nephrotoxic potential of latamoxef (LMOX, 6059-S) was evaluated in male rabbits after combined administration of 500 or 2,000 mg/kg of the compound (ear vein) with subcutaneous injection of furosemide (FUR) at 50 mg/kg. Histological examination of kidney tissues of all animals were performed after 72 hours. Three rabbits were used at each dose level, and comparative studies were performed using several cephalosporins, such as CET and CEZ.Neither LMOX nor CET produced nephrotoxic effects at 500 mg/kg when given in combination with FUR. Although slight elevation of BUN and creatinine in plasma and hyaline casts in lumen of the distal tubules were observed in animals receiving 2,000 mg/kg of LMOX or CET when dosed with FUR, no histological changes were found in renal tissues. Significantly more nephrotoxicity was observed with the treatment of CEZ alone, and this toxicity was augmented in combination with FUR.
II. Concomitant administration of LMOX with intramuscular injection of tobramycin (TOB) was estimated in male rabbits. Rabbits received daily intramuscular injection of TOB at 50 mg/kg for 10 days in combination with single dosing of LMOX (500 or 2,000 mg/kg) on the 8th day after the start of TOB treatment. Three rabbits were used at each dose level, and comparative studies were conducted using CET or CEZ. All rabbits were killed 48 hours after the last injection of TOB and examined histopathologically. Combined administrations of LMOX or CET did not aggravate the nephrotoxicity induced by TOB. However, CEZ enhanced renal injuries produced by TOB injection.