Comparison of vancomycin disposition in rats with normal and abnormal renal functions

Vancomycin levels in the tissues and urine of rats with renal damage were compared with those of control rats. Renal damage was induced by a single intravenous injection of uranyl nitrate. After 5 days, when the plasma urea nitrogen levels had increased 7- to 22-fold, a single intraperitoneal vancomycin injection of 10 mg/kg yielded significantly higher plasma and tissue levels in these rats than in the control rats that did not receive uranyl nitrate. At 73 h after the vancomycin injection, the plasma vancomycin concentration in the rats with renal damage was 1.8 +/- 1.1 microgram/ml (mean +/- standard deviation), whereas in control rats the level had fallen to 0.004 +/- 0.002 microgram/ml. Control rats excreted 50.5% of a single dose in the urine within the 3 days, whereas rats with renal damage excreted only 35.6%. These results indicate that vancomycin pharmacokinetics is affected by renal function in rats. Therefore, the drug should be used very cautiously in patients with impaired renal function. The serum levels must be monitored, and the frequency and size of doses may have to be reduced.