[Modification of vancomycin nephrotoxicity by other antibiotics in rats].
Vancomycin (VCM) was intravenously administered to rats for 14 days at doses of 150 mg/kg/day and 250 mg/kg/day alone or in combination with 1,000 mg/kg/day of latamoxef (LMOX), flomoxef (FMOX) or cefpirome (CPR) or 250 mg/kg/day of fosfomycin (FOM), and the influences of combined antibiotics on the VCM-induced renal damage were studied. The renal impairment caused by VCM alone was, morphologically, demonstrated mainly as regeneration of tubular epithelium: slight regeneration was observed in a half of rats administered 150 mg/kg/day and slight to extensive regeneration in all the rats administered 250 mg/kg/day. Clinical examinations found apparent increases in urinary LDH and MDH activities in rats administered 250 mg/kg/day, thus showing a good correlation with renal pathological changes. In addition, increase in kidney weight and increase in urinary NAG activity were noted, while changes in plasma urea-N and creatinine were mild, and gamma-GTP activity and protein in urine could not be used as a parameter of the renal impairment. The slight renal impairment as noted in rats administered VCM 150 mg/kg/day alone was not observed at all when LMOX or FMOX was administered concomitantly, and less pronounced even when FOM was administered concomitantly. When CPR was administered concomitantly, the changes were the same as those observed with VCM alone. The renal impairment in rats administered VCM 250 mg/kg/day was apparently less severe when combined with LMOX, FMOX and FOM than that in rats administered VCM alone, and this was supported by apparent reduction of clinical examination values as the parameter of VCM-induced nephrotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)
Itoh
F
F
Developmental Research Laboratories, Shionogi Co., & Ltd.
Sato
K
K
Harauchi
T
T
Hirata
M
M
Mizushima
Y
Y
D000818:Animals; D002511:Cephalosporins / Q000008:administration & dosage* / Q000494:pharmacology; D004359:Drug Therapy, Combination; D007668:Kidney / Q000187:drug effects*; D008297:Male; D009070:Moxalactam / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014640:Vancomycin / Q000009:adverse effects*; D000097572:Cefpirome
D002511:Cephalosporins; D009070:Moxalactam; D014640:Vancomycin; D000097572:Cefpirome; C045693:flomoxef