Pharmacokinetics of vancomycin in patients with severely impaired renal function

Abstract

The pharmacokinetics of 1 g dose of intravenous vancomycin was studied in 8 patients with severe renal failure. Serum vancomycin levels were determined by fluorescence polarization immunoassay. After single dose of vancomycin peak concentrations ranged from 37.8 mu g.ml(-1) to 109.3 mu g. ml(-1) (mean 64.9 +/- 21.7 mu g.ml(-1)). Vancomycin trough concentration 168h after administration of the antibiotic ranged from 2.23 mu g.ml(-1) to 11.42 mu g.ml(-1) (mean 6.55 +/- 2.8 mu g.ml(-1)). The data were analyzed using a PCNONLINE computer program, and in all patients a triexponential model described how concentrations decreased in time. Three-compartment parameters obtained from the 8 patients were t(1/2) alpha = 0.312 +/- 0.242 h, t(1/2) beta 6.012 +/- 5.36 h, and t(1/2) gamma = 131.0 +/- 46.7 h. Vd = 0.158 +/- 0.121 1.kg(-1), Vdss = 0.920 +/- 0.248 1.kg(-1) and total Cl = 0.10 +/- 0.049 1.h(-1) per kg of weight. Between 1.5% and 21.2% of the administered vancomycin dose was eliminated during hemodialysis. The dialysis clearance of vancomycin ranged from 50.6 ml.min(-1) to 76.8 ml.min(-1) (average: 62.4 +/- 10.4 ml.min(-1)). However, after dialysis plasma concentrations returned to pre-dialysis values. In accordance to our kinetic study 1 g of vancomycin given every 7 days is adequate treatment for methicillin-resistant Staphylococcus aureus infections in patients with severe renal failure whose creatinine clearance is lower than 10 ml.min(-1).