title: Elimination of meropenem by continuous hemo(dia) filtration: an in vitro one-compartment model.
abstract: Meropenem is a carbapenem antibiotic with a wide spectrum of activity against most gram positive and gram negative bacteria including anaerobes. Dose adjustments are necessary during continuous renal replacement therapies of acute renal failure. This in vitro study was conducted to investigate the influence of different filter materials, surface areas (AN-69 0.6 m2 and 0.9 m2, polysulfone 0.75 m2, polyamide 0.6 m2), and increasing flow rates (from 3.3 - 26.7 ml/min) on the elimination of meropenem in an in vitro continuous hemo(dia)filtration model. Meropenem was measured using HPLC with UV-detection. While the clearance increased proportionally to increasing dialysate flow rates in filters with a surface area of 0.9 m2, a peak clearance was reached in the small filters at flow rates of 10.0 ml/min (polyamide 0.6 m2) and 18.3 ml/min (AN-69 0.6 m2), when tested under the same conditions. This indicated incomplete dialysate saturation due to the diminished time available for meropenem to equilibrate with the dialysate solution. No adsorption to either of the tested membranes was detected. Dosage recommendations derived from clinical studies might be appropriate when different filter materials, but similar operational settings of the continuous replacement therapy, are applied. Reduction of the recommended dose might be necessary, when renal replacement therapies with lower flow rates and/or filters with smaller surface areas are carried out.
authors.affiliation: Department of Anaesthesiology, Eberhard-Karls-University Tuebingen, Germany. tschroeder@rics.bwh.harvard.edu
authors.forename: T H
authors.initials: TH
authors.lastname: Schroeder
authors.forename: W A
authors.initials: WA
authors.lastname: Krueger
authors.forename: M
authors.initials: M
authors.lastname: Hansen
authors.forename: E
authors.initials: E
authors.lastname: Hoffmann
authors.forename: H J
authors.initials: HJ
authors.lastname: Dieterich
authors.forename: K
authors.initials: K
authors.lastname: Unertl
mesh_terms: D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D017583:Hemodiafiltration; D006801:Humans; D066298:In Vitro Techniques; D008567:Membranes, Artificial; D000077731:Meropenem; D009757:Nylons; D011108:Polymers; D013450:Sulfones; D013845:Thienamycins / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D008567:Membranes, Artificial; D009757:Nylons; D011108:Polymers; D013450:Sulfones; D013845:Thienamycins; C017662:polysulfone P 1700; D000077731:Meropenem