This study examined the pharmacokinetics of arbekacin during continuous venovenous hemodiafiltration (CVVHDF) and assessed the pharmacodynamics to consider arbekacin dosage adaptation in CVVHDF. Arbekacin was administered by 0.5-h infusion once daily, using a polymethyl methacrylate membrane hemofilter, to three critically ill patients undergoing CVVHDF; the flow rates were 0.8l/h for the filtrate and 0.6l/h for the dialysate. The drug concentrations in plasma and in the filtrate-dialysate were determined using a fluorescence polarization immunoassay and analyzed pharmacokinetically. The average sieving coefficient of arbekacin was 0.739 and the average drug clearance by CVVHDF was 1.03l/h. A pharmacokinetic model with three compartments (1, central; 2, peripheral; 3, filtrate-dialysate side hemofilter) accurately reflected the concentration-time data for both plasma and filtrate-dialysate. The pharmacokinetic model assessed the pharmacodynamic profile of arbekacin once-daily regimens (0.5-h infusions) at filtrate-dialysate flow rates of 1.4 and 2.8l/h, and demonstrated that only the 150-mg and 200-mg regimens achieved an effective target range for C max (9–20µg/ml), suggesting that empirical dosages lower than the usual 150–200mg should be avoided in patients undergoing CVVHDF. The minimum regimens needed to achieve an effective pharmacodynamic target for the free C max /MIC ratio (>8) were 75mg for an MIC of 0.5µg/ml, 200 mg for an MIC of 2µg/ml, and 400mg for an MIC of 4µg/ml. These results will help us to better understand the pharmacokinetics of arbekacin during CVVHDF, while also helping in the selection of the appropriate arbekacin regimens, based on a pharmacodynamic assessment, for patients receiving this renal replacement therapy.