Binding of warfarin by human albumin in the presence of a perfluorochemical blood substitute.
The effect of a perfluorochemical blood substitute on ligand binding by human albumin was examined using warfarin as a model drug. Binding of warfarin by four per cent human albumin solutions diluted with either buffer or blood substitute, and by blood substitute diluted with buffer was examined. Solutions containing 2 or 10 micrograms/ml warfarin were quantitated by liquid scintillation counting using 14C-warfarin. The per cent warfarin free at room temperature was determined by centrifugation followed by supernatant ultrafiltration. Warfarin was weakly bound by the blood substitute and the overall effect of albumin dilution with the blood substitute was an increase in per cent warfarin free. Blood substitute binding of warfarin may explain the decrease of per cent warfarin free observed when albumin solutions were diluted to 50 and 75% v/v with blood substitute rather than buffer. However, the per cent warfarin free increased when albumin solutions were diluted to 25% v/v with blood substitute rather than buffer. The fraction free increased by 39.0% and 30.4% at total warfarin concentrations of 2 and 10 micrograms/ml, respectively. This relative increase in per cent warfarin free may be the result of a direct and/or indirect displacement of albumin bound warfarin by a component(s) of the blood substitute.
D001802:Blood Substitutes / Q000494:pharmacology*; D003956:Dialysis; D004338:Drug Combinations / Q000494:pharmacology; D005466:Fluorocarbons / Q000494:pharmacology*; D006801:Humans; D006895:Hydroxyethyl Starch Derivatives; D066298:In Vitro Techniques; D011485:Protein Binding / Q000187:drug effects; D012709:Serum Albumin / Q000378:metabolism*; D014462:Ultrafiltration; D014859:Warfarin / Q000378:metabolism*
D001802:Blood Substitutes; D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D012709:Serum Albumin; D014859:Warfarin; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination