European Journal of Medicinal Chemistry 2009-01-01

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

Xiaofan Sui, Jin Sun, Haiyan Li, Yongjun Wang, Jianfang Liu, Xiaohong Liu, Wenping Zhang, Lijiang Chen, Zhonggui He, Xiaofan Sui, Jin Sun, Haiyan Li, Yongjun Wang, Jianfang Liu, Xiaohong Liu, Wenping Zhang, Lijiang Chen, Zhonggui He

Index: Eur. J. Med. Chem. 44 , 4455-60, (2009)

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Abstract

We developed an improved Lombardeo's method (J. Med. Chem., 2004) for prediction of VD ss in human. With Elog D substituted by log k IAM, together with f i (7.4) (the fraction of compound ionized at pH 7.4) and log f u (logarithmic fraction of compound unbound in plasma), the predictive equation of f ut (the fraction of the compound unbound in tissues) for the 121 compounds was built, predictive VD ss 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.