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Korzekwa K , Nagar S
Drug Distribution Part 2. Predicting Volume of Distribution from Plasma Protein Binding and Membrane Partitioning
Pharm Res. 2017 Mar;34(3) :544-551
PMID: 27966088    PMCID: PMC5285473   
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Abstract
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These results suggest that Vss can be predicted for most drugs from plasma protein binding and microsomal partitioning.
Notes
1573-904x Korzekwa, Ken Nagar, Swati ORCID: http://orcid.org/0000-0003-2667-7063 R01 GM104178/GM/NIGMS NIH HHS/United States R01 GM114369/GM/NIGMS NIH HHS/United States Journal Article United States Pharm Res. 2017 Mar;34(3):544-551. doi: 10.1007/s11095-016-2086-y. Epub 2016 Dec 13.