@article {Waller203, author = {C L Waller and M V Evans and J D McKinney}, title = {Modeling the cytochrome P450-mediated metabolism of chlorinated volatile organic compounds.}, volume = {24}, number = {2}, pages = {203--210}, year = {1996}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity relationship (3D-QSAR) paradigm, has been used to analyze the metabolic rates, as intrinsic clearance, of a series of chlorinated volatile organic compounds (VOCs). A comparison between 3D-QSAR and conventional Hansch-type QSAR is provided. To develop predictive 3D-QSARs for metabolism, the standard CoMFA model based on steric and electrostatic potential fields must be supplemented with hydropathic and molecular orbital information also in the form of three-dimensional fields. A mechanistic interpretation of chlorinated VOC metabolism by cytochrome P450 isozymes is provided as a rationalization for the inclusion of multiple fields in the CoMFA 3D-QSAR model. Models of this type have practical utility in the development of generalized physiologically-based pharmacokinetic models, as well as the rational, structure-based, design and/or selection of compounds for use in the in vivo and in vitro metabolic studies.}, issn = {0090-9556}, URL = {https://dmd.aspetjournals.org/content/24/2/203}, eprint = {https://dmd.aspetjournals.org/content/24/2/203.full.pdf}, journal = {Drug Metabolism and Disposition} }