VANCOMYCIN IN RABBITS - PHARMACOKINETICS, EXTRA-VASCULAR DIFFUSION, RENAL EXCRETION AND INTERACTIONS WITH FUROSEMIDE

Abstract

The pharmacokinetics, renal excretion, protein binding and extravascular diffusion of vancomycin in rabbits were studied. The effects of furosemide on these different parameters also were investigated. One observed a T1/2 [half-life] of 55 min and protein binding of 65% as determined in vitro by equilibrium dialysis. Vancomycin appeared to be secreted by renal tubules (fractional excretion: 177 .+-. 44%). In vitro, furosemide (5 .mu.g/ml) slightly decreased the vancomycin protein binding (from 65 to 57%). Furosemide significantly increased the renal excretion of vancomycin through a tubular process without any effect on the filtered load. Vancomycin appeared slowly and at low concentrations in the extravascular fluid. The extravascular concentrations were higher when the antibiotic was administered by a 6-h continuous infusion than when given by a 20 min infusion of the same dose. The in vivo antibacterial effect of vancomycin apparently could be enhanced by prolonged infusion. Furosemide has only a small effect on the kinetics of vancomycin.