Acta Pharm. 62 (2012) 305-323


full paper

Original research paper


Quantitative structure-pharmacokinetic relationship (QSPkR) analysis of the volume of distribution values of anti-infective agents from J group of the ATC classification in humans


1 Department of Pharmacy, Sultan Qaboos University Hospital, PO Box 38, Al Khod, Muscat 123, Oman

2 QSAR and Computer Chemical Laboratories, A.P.S. University, Rewa-486003, India

Accepted June 12, 2012

In this study, a quantitative structure-pharmacokinetic relationship (QSPkR) model for the volume of distribution (Vd) values of 126 anti-infective drugs in humans was developed employing multiple linear regression (MLR), artificial neural network (ANN) and support vector regression (SVM) using theoretical molecular structural descriptors. A correlation-based feature selection (CFS) was employed to select the relevant descriptors for modeling. The model results show that the main factors governing Vd of anti-infective drugs are 3D molecular representations of atomic van der Waals volumes and Sanderson electronegativities, number of aliphatic and aromatic amino groups, number of beta-lactam rings and topological 2D shape of the molecule. Model predictivity was evaluated by external validation, using a variety of statistical tests and the SVM model demonstrated better performance compared to other models. The developed models can be used to predict the Vd values of anti-infective drugs.


Keywords: QSPkR, QSPR, structure pharmacokinetic relationship, volume of distribution, ANN, SVM, CFS