Pharmacokinetics of Intravenous Vancomycin in Patients with End-Stage Renal Failure

Abstract

The pharmacokinetics of a 500-mg dose of i.v. vancomycin were studied in six Chinese patients with end-stage renal failure. Serum vancomycin concentrations were determined by high-performance liquid chromatography. Observed peak and trough (at 168 h postinfusion) concentrations were in the range of 14.2-35.0 micrograms/ml and 2.8-5.5 micrograms/ml, respectively. The data were analyzed using the PCNONLIN. In all six patients, the data could be fitted well by both the biexponential and triexponential models, but in three patients the latter model provided a better fit. Two-compartment pharmacokinetic parameters obtained from the six patients were t 1/2 alpha 1.13 +/- 0.25 h (mean +/- SEM), t 1/2 beta 121.3 +/- 8.2 h, Vc 0.45 +/- 0.09 L/kg, Vss 1.00 +/- 0.12 L/kg, ClT 5.90 +/- 0.69 ml/kg/h, and the calculated Cmax 25.0 +/- 6.1 micrograms/ml. The mean vancomycin serum protein binding was 18.5 +/- 12.0% as compared with a mean of 46.0% in pooled serum from normal controls. Hemodialysis had no significant effect on vancomycin protein binding or clearance. On the basis of our kinetic study, 500 mg of vancomycin given every seven days is probably adequate treatment for methicillin resistant Staphylococcus aureus infection in end-stage renal failure patients, but further clinical studies are necessary to confirm this.