RT Journal Article
SR Electronic
T1 Modeling the cytochrome P450-mediated metabolism of chlorinated volatile organic compounds.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 203
OP 210
VO 24
IS 2
A1 C L Waller
A1 M V Evans
A1 J D McKinney
YR 1996
UL http://dmd.aspetjournals.org/content/24/2/203.abstract
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.