Pharmacokinetics of antimicrobial agents in anuric patients during continuous venovenous haemofiltration

The optimal drug dosing in anuric patients undergoing continuous haemofiltration is a difficult task. More pharmacokinetic data is needed to derive practical guidelines for dosage adjustments.

Drug elimination of various antimicrobial agents (amikacin, amoxycillin, ceftazidime, ciprofloxacin, flucloxacillin, imipenem, netilmicin, penicillin G, piperacillin, sulphamethoxazole, tobramycin, vancomycin) was studied in 24 patients with acute renal failure treated by pump-assisted continuous venovenous haemofiltration (CVVH). Concentrations of serial blood and ultrafiltrate samples were determined by HPLC or by fluorescence polarization immunoassay. Total body clearance (CL) and haemofilter clearance (CLf) rates were determined by standard model-independent equations. Data from published literature on fractions not bound to proteins (fu), non-renal drug clearance fractions (Qo), and normal clearance values (CLn) were used to derive a pharmacokinetic model, taking into account drug removal by ultrafiltration and by non-renal clearance.

A total of 37 treatment periods was studied. Blood flow through the haemofilters was 100 ml/min resulting in an average ultrafiltrate flow rate (UFR) of 13.2 +/- 4.6 (range 3.2-22.1) ml/min. Acceptable correlations of calculated and measured haemofilter clearances and total body clearances were obtained.

Total body clearance in anuric patients during CVVH is predictable from drug properties, which are generally known. The individual dosage requirements may be calculated by multiplying Qo + fu.UFR/CLn with the dose considered appropriate in the absence of renal impairment.