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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) 34:544-551.
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.
Publication Date: 2017-03-01.
PMCID: PMC5285473
Last updated on Monday, May 04, 2020