Pharmacokinetics of antimicrobial agents in anuric patients during continuous venovenous haemofiltration |
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Authors: | Joos, B. Schmidli, M. Keusch, G. |
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Affiliation: | Department of Medicine, University Hospital Zürich, Switzerland |
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Abstract: | 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 (CLf) rateswere determined by standard model-independent equations. Datafrom published literature on fractions not bound to proteins(fu), non-renal drug clearance fractions (Qo) and normal clearancevalues (CLn) 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 3.222.1) 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 Qo+fu UFR/CLnwith the dose considered appropriate in the absence of renalimpairment. |
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Keywords: | acute renal failure antimicrobial agents continuous venovenous haemofiltration drug dosage pharmacokinetics |
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