title: Pharmacokinetics and pharmacodynamics of once-daily arbekacin during continuous venovenous hemodiafiltration in critically ill patients.
abstract: 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 0.8 l/h for the filtrate and 0.6 l/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 1.03 l/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 2.8 l/h, and demonstrated that only the 150-mg and 200-mg regimens achieved an effective target range for C(max) (9-20 microg/ml), suggesting that empirical dosages lower than the usual 150-200 mg 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 75 mg for an MIC of 0.5 microg/ml, 200 mg for an MIC of 2 microg/ml, and 400 mg for an MIC of 4 microg/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.
authors.affiliation: Department of Clinical Pharmacotherapy, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minamiku, Hiroshima, 734-8551, Japan. ikawak@hiroshima-u.ac.jp
authors.forename: Kazuro
authors.initials: K
authors.lastname: Ikawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Morikawa
authors.forename: Hidemichi
authors.initials: H
authors.lastname: Suyama
authors.forename: Kayo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Takao
authors.initials: T
authors.lastname: Yamanoue
mesh_terms: D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D003198:Computer Simulation; D016638:Critical Illness; D003982:Dibekacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D006440:Hemofiltration; D006801:Humans; D008826:Microbial Sensitivity Tests; D008875:Middle Aged
chemical_list: D000890:Anti-Infective Agents; D003982:Dibekacin; C031986:arbekacin