title: Extracorporeal elimination of large concentrations of tirofiban by zero-balanced ultrafiltration during cardiopulmonary bypass: an in vitro investigation.
abstract: The short-acting platelet glycoprotein IIb/IIIa antagonist tirofiban is beneficial when used in the context of cardiac surgery. Tirofiban has an elimination half-life of 2 h. Renal failure prolongs the half-life and continues inhibition of platelet aggregation refractory to transfusions of platelets. Extracorporeal elimination is necessary to prevent excessive hemorrhage in this condition. We assessed the elimination of tirofiban by hemofiltration in an in vitro model of cardiopulmonary bypass (CPB). Two hemofilters and one plasmapheresis filter were assessed. Three separate filters of each type were tested serially. The CPB circuit was primed with a total volume of 1000 mL. Tirofiban was added to a calculated concentration of 200 ng/mL. Portions of 50 mL of filtrate were retrieved from the dialyzer, and equal amounts of fluid were substituted in the circuit. After each filtration, the tirofiban blood level was analyzed. The procedure was repeated 16 times. Peak tirofiban concentrations ranged from 160 to 260 ng/mL. The elimination of tirofiban followed an exponential decay curve with fast clearance of the large therapeutic concentrations of 250 to 50 ng/mL. The subsidence coefficient b revealed no significant differences in elimination between the filter systems. These data suggest that ultrafiltration is an effective means for extracorporeal elimination of therapeutic levels of tirofiban.
authors.affiliation: *Department of Anesthesia, Deutsches Herzzentrum Berlin, Berlin, Germany; †Department of Cardiology, Flinders Medical Centre, Bedford Park, Australia; ‡Department of Perfusion, Deutsches Herzzentrum Berlin, Berlin, Germany; §Department of Anesthesia and Intensive Care Medicine, Charite, Campus Virchow, Berlin, Germany; ∥Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; and ¶Institute of Clinical Pharmacology, Carl Gustav Carus Faculty of Medicine, University of Technology, Dresden, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Koster
authors.forename: Derek
authors.initials: D
authors.lastname: Chew
authors.forename: Frank
authors.initials: F
authors.lastname: Merkle
authors.forename: Marcus
authors.initials: M
authors.lastname: Gruendel
authors.forename: Michael
authors.initials: M
authors.lastname: Jurmann
authors.forename: Hermann
authors.initials: H
authors.lastname: Kuppe
authors.forename: Rainhard
authors.initials: R
authors.lastname: Oertel
mesh_terms: D002315:Cardiopulmonary Bypass; D005112:Extracorporeal Circulation; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000097:blood*; D000077466:Tirofiban; D014443:Tyrosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood*; D014462:Ultrafiltration
chemical_list: D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; D000077466:Tirofiban