Intrarenal distribution of vancomycin in endotoxemic rats

We previously observed that the intrarenal distribution of aminoglycosides was modified by Escherichia coli endotoxin in the absence of any major renal physiological disturbance or histological changes. In the present study, we evaluated the role of E. coli endotoxin on the intrarenal distribution of vancomycin. At the beginning of the experiment, female Sprague-Dawley rats were infused intravenously with saline (control) or endotoxin (0.25 mg/kg) during 15 min. Thereafter, saline was constantly infused for the following 4 h. Two hours after the beginning of the infusion, animals were injected intravenously with a single dose of vancomycin (20 mg/kg). The drug levels in serum; renal cortex, medulla, and papilla; and urine were evaluated from 0.08 to 24 h after injection. Analysis of the area under the curve of the drug concentration in the different kidney components versus time showed a higher accumulation of vancomycin in the renal cortex and medulla in the endotoxin-infused rats than in the normal rats (P less than 0.01). Endotoxin was associated with an increase in the half-life in serum (P less than 0.01) and a lower elimination rate constant. The total clearance of vancomycin from plasma was significantly decreased in endotoxin-treated rats (P less than 0.01). These results demonstrate that endotoxin modifies the renal handling of vancomycin.