Turner, Joseph V., Glass, Beverly D., and Agatonovic-Krustrin, Snezana (2003) Prediction of drug bioavailability based on molecular structure. Analytica Chimica Acta, 485 (1). pp. 89-102.

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Abstract

Oral dosing is the most common method of drug administration, and final plasma concentrations of the drug depend upon its bioavailability. In the current study, a quantitative structure–pharmacokinetic relationship (QSPR) was developed for a diverse range of compounds to allow prediction of drug bioavailability. Bioavailability data for 169 compounds was taken from the literature, and from the molecular structures 94 theoretical descriptors were generated. Stepwise regression was employed to develop a regression equation based on 159 training compounds, and predictive ability was tested on 10 compounds reserved for that purpose. The final regression equation included eight descriptors that represented electronic, steric, hydrophobic and constituent parameters of the drug molecules, all of which could be related to solubility and partitioning properties. Predicted bioavailability for the training set agreed more closely for drugs exhibiting mid-range literature bioavailability values. A correlation of 0.72 was achieved for test set bioavailability predictions when compared with literature values. The structure–pharmacokinetic relationship developed in the current study highlighted solubility and partitioning characteristics that may be useful in designing drugs with appropriate bioavailability.

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