Protective effect of piperacillin against nephrotoxicity of cephaloridine and gentamicin in animals

Author:

Hayashi T1,Watanabe Y1,Kumano K1,Kitayama R1,Yasuda T1,Saikawa I1,Katahira J1,Kumada T1,Shimizu K1

Affiliation:

1. Research Laboratory, Toyama Chemical Co., Ltd., Japan.

Abstract

The protective effect of piperacillin against the nephrotoxicity of cephaloridine and gentamicin was examined in experimental animals. In rabbits, piperacillin was infused at a dose of 1 mg/kg (body weight) per min over 225 min and cephaloridine (300 mg/kg) was intravenously administered as a bolus 45 min after the start of a drip infusion. Blood urea nitrogen, serum creatinine, and N-acetyl-beta-D-glucosaminidase (NAG) in urine were measured as the renal toxicological parameters before and 24 h after cephaloridine dosing. Although the single administration of cephaloridine significantly elevated these parameters, the elevation was prevented by the concomitant administration of piperacillin. The protective effect of piperacillin was superior to those of cephalothin and fosfomycin. In rats, piperacillin (1,000 mg/kg) was intravenously administered and immediately followed by the intramuscular administration of gentamicin (100 mg/kg) every 24 h for 5 days. When piperacillin was concomitantly administered with gentamicin, the elevations of blood urea nitrogen, serum creatinine, and urinary NAG were significantly lower than when gentamicin was given alone. The concomitant administration of piperacillin resulted in a significant protective effect against the nephrotoxicity of cephaloridine in rabbits and of gentamicin in rats. Histopathological observation also supported the protective effect of piperacillin. The protective mechanism of piperacillin might be the inhibition of transport from the peritubular side to tubular cells for cephaloridine and from both the peritubular and luminal sides for gentamicin.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Reference31 articles.

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2. Protective effect of frusemide in acute tubular necrosis and acute renal failure;Bailey R. R.;Clin. Sci. Mol. Med.,1973

3. Barza M. V. Pinn P. Tanguay and T. Murray. 1978. Nephrotoxicity of newer cephalosporins and aminoglycosides alone and in combination in a rat model. J. Antimicrob. Chemother. 4(Suppl. A):59-68.

4. Benner E. J. 1970. Renal damage associated with prolonged administration of ampicillin cephaloridine and cephalothin p. 417-420. Antimicrob. Agents Chemother. 1969.

5. Protection from gentamicin nephrotoxicity by cephalothin and carbenicillin;Bloch R.;Antimicrob. Agents Chemother.,1979

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