title: Drug Distribution Part 2. Predicting Volume of Distribution from Plasma Protein Binding and Membrane Partitioning.
abstract: Volume of distribution is an important pharmacokinetic parameter in the distribution and half-life of a drug. Protein binding and lipid partitioning together determine drug distribution.
  
  
  
  Here we present a simple relationship that estimates the volume of distribution with the fraction of drug unbound in both plasma and microsomes. Model equations are based upon a two-compartment system and the experimental fractions unbound in plasma and microsomes represent binding to plasma proteins and cellular lipids, respectively.
  
  
  
  The protein and lipid binding components were parameterized using a dataset containing human in vitro and in vivo parameters for 63 drugs. The resulting equation explains ~84% of the variance in the log of the volume of distribution with an average fold-error of 1.6, with 3 outliers.
  
  
  
  These results suggest that Vsscan be predicted for most drugs from plasma protein binding and microsomal partitioning.
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N Broad Street, Philadelphia, Pennsylvania, 19140, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Korzekwa
authors.affiliation: Department of Pharmaceutical Sciences, Temple University School of Pharmacy, 3307 N Broad Street, Philadelphia, Pennsylvania, 19140, USA. swati.nagar@temple.edu.
authors.forename: Swati
authors.identifier: 0000-0003-2667-7063
authors.initials: S
authors.lastname: Nagar
mesh_terms: D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D002626:Chemistry, Pharmaceutical; D006207:Half-Life; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D008954:Models, Biological; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D010599:Pharmacokinetics; D010743:Phospholipids / Q000378:metabolism; D011485:Protein Binding; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014018:Tissue Distribution
chemical_list: D001798:Blood Proteins; D004364:Pharmaceutical Preparations; D010743:Phospholipids
keywords: microsomal partitioning; volume of distribution