PT  - JOURNAL ARTICLE
AU  - Waller, C L
AU  - Evans, M V
AU  - McKinney, J D
TI  - Modeling the cytochrome P450-mediated metabolism of chlorinated volatile organic compounds.
DP  - 1996 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 203--210
VI  - 24
IP  - 2
4099  - http://dmd.aspetjournals.org/content/24/2/203.short
4100  - http://dmd.aspetjournals.org/content/24/2/203.full
SO  - Drug Metab Dispos1996 Feb 01; 24
AB  - 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.