Penetration of cefazolin into normal and osteomyelitic canine cortical bone

Abstract

The ability of cefazolin to cross the capillary membrane and its concentrations in the interstitial fluid spaces were studied in normal and osteomyelitic canine bone. The maximum extraction after a single capillary passage and the net extraction after 3 min, determined with triple-tracer indicator-dilution techniques, demonstrated that cefazolin readily traversed the capillaries of normal and osteomyelitic bone. These studies suggest that the altered pathophysiology of osteomyelitic tissue and the complex diffusional characteristics of cefazolin enhanced the ability of this agent to cross the endothelial cells lining the capillaries of osteomyelitic bone. Volume of distribution studies demonstrated that cefazolin was distributed in the plasma and interstitial fluid spaces of normal cortical bone. Although these spaces were increased 330 and 941% in osteomyelitic tissue, the distribution of cefazolin increased proportionally. There was a direct correlation between the calculated concentrations of cefazolin in the interstitial fluid spaces of normal and osteomyelitic cortical bone and the simultaneous serum levels in animals in which a steady-state equilibrium had been achieved. These studies suggest that a physiological barrier or concentration gradient for cefazolin does not exist in normal or osteomyelitic bone. Cefazolin can cross the capillary membranes of bone and achieve bactericidal concentrations in the interstitial fluid space of normal and osteomyelitic tissue.