VANCOMYCIN DOSING IN HEMODIALYSIS-PATIENTS AND BAYESIAN ESTIMATE OF INDIVIDUAL PHARMACOKINETIC PARAMETERS

A dose reduction of vancomycin to 1000 mg once a week usually is recom mended for haemodialysis patients. Our modified dosing schedule consis ts of a loading dose of 1000 mg and a maintenance dose of 500 mg admin istered 3 times a week after haemodialysis. Different vancomycin regim ens 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 re gimen was significantly lower than in 17 patients strictly treated by the modified schedule (7 +/- 4 versus 17 +/- 8 mg/L; p = 0.001). The c orresponding 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). Hig h-flux dialysers were not used in the conventional dosage group but fo r 30 percent of the procedures in the modified dosage group, where the vancomycin one week average elimination half-life was 66 hours (+/- 1 8) and the volume of distribution 50 litres (+/- 5). As compared to th e bayesian programme, NONMEM calculated comparable pharmacokinetic par ameters but could be applied only in 5 cases with a sufficient number of concentration measurements. Ototoxicity occurred in 1 patient, wher eas vancomycin treatment was judged as ineffective against infection i n 5 of the 39 patients. Their, troughs were below 15 mg/L. The apparen t tendency toward underdosage can be avoided by giving haemodialysis p atients the modified vancomycin schedule (3 x 500 mg/week) with the hi gher trough levels considered therapeutic (10 - 20 mg/L).