Prediction of volume of distribution values in human using immobilized artificial membrane partitioning coefficients, the fraction of compound ionized and plasma protein binding data.

We developed an improved Lombardeo's method (J. Med. Chem., 2004) for prediction of VDss in human. With ElogD substituted by logkIAM, together with fi (7.4) (the fraction of compound ionized at pH 7.4) and logfu (logarithmic fraction of compound unbound in plasma), the predictive equation of fut (the fraction of the compound unbound in tissues) for the 121 compounds was built, predictive VDss was further obtained from the Øie–Tozer equation. Our model could be applicable to structurally diverse compounds, including acids, bases, neutrals, and ampholytes. Interior and exterior validation results indicated the model had a robust predictive ability. Compared to the Lombardeo's and Hollósy's (J. Med. Chem., 2006) methods, our model can be generally applicable with better predictive accuracy.