Vancomycin Dosing in Haemodialysis Patients and Bayesian Estimate of Individual Pharmacokinetic Parameters

Abstract

A dose reduction of vancomycin to 1000 mg once a week usually is recommended for haemodialysis patients. Our modified dosing schedule consists of a loading dose of 1000 mg and a maintenance dose of 500 mg administered 3 times a week after haemodialysis. Different vancomycin regimens were retrospectively evaluated by therapeutic drug monitoring and bayesian parameter estimates in 39 dialysis patients. The mean (± SD) trough level in 7 patients receiving only the conventional dosage regimen was significantly lower than in 17 patients strictly treated by the modified schedule (7 ± 4 versus 17 ± 8 mg/L; p = 0.001). The corresponding peaks were low in both groups and no different (23 ± 10 versus 27 ± 12 mg/L). The one week average vancomycin clearance was significantly lower in the conventional dosage group compared to the modified dosage group (6 ± 3 versus 10 ± 3 ml/min; p = 0.001). High-flux dialysers were not used in the conventional dosage group but for 30 percent of the procedures in the modified dosage group, where the vancomycin one week average elimination half-life was 66 hours (± 18) and the volume of distribution 50 litres (± 5). As compared to the bayesian programme, NONMEM calculated comparable pharmacokinetic parameters but could be applied only in 5 cases with a sufficient number of concentration measurements. Ototoxicity occurred in 1 patient, whereas vancomycin treatment was judged as ineffective against infection in 5 of the 39 patients. Their troughs were below 15 mg/L. The apparent tendency toward underdosage can be avoided by giving haemodialysis patients the modified vancomycin schedule (3 × 500 mg/week) with the higher trough levels considered therapeutic (10 - 20 mg/L).