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 VD(ss) in human. With ElogD substituted by logk(IAM), together with f(i (7.4)) (the fraction of compound ionized at pH 7.4) and logf(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.
Sui
Xiaofan
X
Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Sun
Jin
J
Li
Haiyan
H
Wang
Yongjun
Y
Liu
Jianfang
J
Liu
Xiaohong
X
Zhang
Wenping
W
Chen
Lijiang
L
He
Zhonggui
Z
D001798:Blood Proteins / Q000378:metabolism*; D002627:Chemistry, Physical; D003198:Computer Simulation; D006801:Humans; D008567:Membranes, Artificial; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D014018:Tissue Distribution
D001798:Blood Proteins; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations