PHARMACOKINETICS OF ANTIMICROBIAL AGENTS IN ANURIC PATIENTS DURING CONTINUOUS VENOVENOUS HEMOFILTRATION

Background. The optimal drug dosing in anuric patients undergoing cont inuous haemofiltration is a difficult task. More pharmacokinetic data is needed to derive practical guidelines for dosage adjustments. Metho ds. Drug elimination of various antimicrobial agents (amikacin, amoxyc illin, ceftazidime, ciprofloxacin, flucloxacillin,, imipenem, netilmic in, penicillin G, piperacillin, sulphamethoxazole, tobramycin, vancomy cin) was studied in 24 patients with acute renal failure treated by pu mp-assisted continuous venovenous haemofiltration (CVVH). Concentratio ns of serial blood and ultrafiltration samples were determined by HPLC or by fluorescence polarization immunoassay, Total body clearance (CL ) and haemofilter clearance (CL(f)) rates were determined by standard model-independent equations. Data from published literature on fractio ns not bound to proteins (f(u)), non-renal drug clearance fractions (Q (o)), and normal clearance values (CL(n)) were used to derive a pharma cokinetic model, taking into account drug removal by ultrafiltration a nd by non-renal clearance. Results. A total of 37 treatment periods wa s studied. Blood flow through the haemofilters was 100 ml/min resultin g in an average ultrafiltrate flow rate (UFR) of 13.2 +/- 4.6 (range 3 .2-22.1) ml/min. Acceptable correlations of calculated aad measured ha emofilter clearances and total body clearances were obtained. Conclusi ons. Total body clearance in anuric patients during CVVH is predictabl e from drug properties, which art generally known. The individual dosa ge requirements may be calculated by multiplying Q(o) + f(u) . UFR/CL( n) with the dose considered appropriate in the absence of renal impair ment.