Pharmacokinetics of antimicrobial agents in anuric patients during continuous venovenous haemofiltration

BACKGROUND.: The optimal drug dosing in anuric patients undergoing continuoushaemofiltration is a difficult task. More pharmacokinetic datais needed to derive practical guidelines for dosage adjustments. METHODS.: 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 failuretreated by pump-assisted continuous venovenous haemofiltration(CVVH). Concentrations of serial blood and ultrafiltrate sampleswere determined by HPLC or by fluorescence polarization immunoassay.Total body clearance (CL) and haemofilter clearance (CL_f) rateswere determined by standard model-independent equations. Datafrom published literature on fractions not bound to proteins(f_u), non-renal drug clearance fractions (Q_o) and normal clearancevalues (CL_n) were used to derive a pharmacokinetic model, takinginto account drug removal by ultrafiltration and by non-renalclearance. RESULTS.: A total of 37 treatment periods was studied. Blood flow throughthe haemofilters was 100 ml/min resulting in an average ultrafiltrateflow rate (UFR) of 13.2±4.6 (range 3.2–22.1) ml/min.Acceptable correlations of calculated and measured haemofilterclearances and total body clearances were obtained. CONCLUSIONS.: Total body clearance in anuric patients during CVVH is predictablefrom drug properties, which are generally known. The individualdosage requirements may be calculated by multiplying Q_o+f_u UFR/CL_nwith the dose considered appropriate in the absence of renalimpairment.