EFFECTS OF FUROSEMIDE ON EXTRA-VASCULAR DIFFUSION, PROTEIN-BINDING AND URINARY-EXCRETION OF CEPHALOSPORINS AND AMINOGLYCOSIDES IN RABBITS

Abstract

The effects of furosemide on the disposition of cefazolin and gentamicin in rabbits. Protein binding (PB) by ultracentrifugation in vitro and renal excretion and distribution in extravascular fluid (EF) obtained from s.c. tissue cages in vivo were studied. Single i.m. injections of cefazolin (30 mg/kg) and gentamicin (1.5 mg/kg) alone or in combination with furosemide (0.5, 1 and 5 mg/kg) were made. After furosemide injection, blood and EF levels of gentamicin significantly decreased. Cefazolin blood levels were unchanged. Cefazolin appeared in EF earlier and at higher levels, up to 4 h after furosemide injection, than when administered alone. Late cefazolin EF levels (8 and 12 h) were reduced. All the effects were furosemide dose-dependent. Furosemide, in vitro, decreased cefazolin PB from 80 to 50%, but PB of gentamicin remained minimal (0-4%). Furosemide significantly increased the renal excretion of cefazolin and gentamicin without any effect on the glomerular filtration rate. A competitive effect of furosemide on the PB of cephradin and netilmicin was demonstrated in vitro and in vivo. Two kinds of interaction between furosemide and antibiotics are outlined. With protein-bound drugs, furosemide induced a competitive reduction of PB responsible for earlier EF diffusion and increased glomerular filtered load, but induced an increased renal excretion by a tubular process. The latter was the only 1 induced by furosemide on unbound drugs (gentamicin).