title: Determination of drug binding to plasma proteins using competitive equilibrium binding to dextran-coated charcoal.
abstract: A method for determination of drug binding to plasma proteins, which is based on the comparison of drug affinities to plasma proteins and dextran-coated charcoal, is described. The method is free of nonspecific binding feature. The fractions unbound obtained by the charcoal method are in good agreement with values from a traditional ultrafiltration method for various low and highly bound compounds. The method presently requires drug concentrations much less than that of plasma proteins. A possibility of using the method to determine protein binding at an arbitrary drug concentration is discussed. A mechanism of nonspecific binding of drug to ultrafiltration membranes, which yields a good agreement with experimental observations, is suggested.
authors.affiliation: Roche Palo Alto, 3401 Hillview Avenue, Palo Alto, CA 94304, USA. leo.berezh@yahoo.com
authors.forename: Leonid M
authors.initials: LM
authors.lastname: Berezhkovskiy
mesh_terms: D000327:Adsorption / Q000187:drug effects; D000465:Algorithms; D001667:Binding, Competitive / Q000187:drug effects; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D002264:Carboxylic Acids / Q000378:metabolism / Q000493:pharmacokinetics; D002606:Charcoal / Q000737:chemistry / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D003509:Cyclohexanecarboxylic Acids; D003911:Dextrans / Q000737:chemistry / Q000378:metabolism*; D000068736:Duloxetine Hydrochloride; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013058:Mass Spectrometry / Q000379:methods; D009570:Nitriles / Q000378:metabolism / Q000493:pharmacokinetics; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D010726:Phosphodiesterase Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics; D013876:Thiophenes / Q000378:metabolism / Q000493:pharmacokinetics; D014462:Ultrafiltration / Q000379:methods
chemical_list: D001798:Blood Proteins; D002264:Carboxylic Acids; D002606:Charcoal; D003509:Cyclohexanecarboxylic Acids; D003911:Dextrans; D000068736:Duloxetine Hydrochloride; D009570:Nitriles; D004364:Pharmaceutical Preparations; D010726:Phosphodiesterase Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes; C433247:Cilomilast