Vancomycin in rabbits: pharmacokinetics, extravascular 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. We observed a T 1/2 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 micrograms/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-hr continuous infusion than when given by a 20-min infusion of the same dose. Our results suggested that the in vivo antibacterial effect to vancomycin could be enhanced by prolonged infusion. Also, it was demonstrated that furosemide has only a small effect on the kinetics of vancomycin.