title: Prediction of volume of distribution values in human using immobilized artificial membrane partitioning coefficients, the fraction of compound ionized and plasma protein binding data.
abstract: 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.
authors: Department of Biopharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
authors: Xiaofan
authors: X
authors: Sui
authors: Jin
authors: J
authors: Sun
authors: Haiyan
authors: H
authors: Li
authors: Yongjun
authors: Y
authors: Wang
authors: Jianfang
authors: J
authors: Liu
authors: Xiaohong
authors: X
authors: Liu
authors: Wenping
authors: W
authors: Zhang
authors: Lijiang
authors: L
authors: Chen
authors: Zhonggui
authors: Z
authors: He
mesh_terms: 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
chemical_list: D001798:Blood Proteins; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations