Models for Prediction of Volume

Estimation of the volume of distribution in man may be carried out in a number of ways. These methods have recently been reviewed by Obach et al. [60], who carried out a wide-ranging evaluation of a large number of different ways of predicting the human pharmacokinetics of 50 compounds that entered development at Pfizer. One of the simplest methods was reported to be the most reliable. It is based on the assumption that the free-fraction of drug in the plasma in dog and human and 

Both human and dog volumes are in units of L kg-1, and fu is the fraction of the drug unbound in plasma. The method was found to predict within 2-fold for about 80% of the compounds, which spanned about three orders of magnitude in their Vd. Although the dog has been recommended as the best model for predicting volume in man [60], there are also reports indicating that the rat may also be a suitable model [61]. 

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