A human drug metabolism database: potential roles in the quantitative predictions of drug metabolism and metabolism-related drug-drug interactions.
Previous attempts to predict drug metabolism and drug-drug interaction possibilities by deploying databases that house established drug metabolism results have been only marginally successful. Consideration of some of the key issues and concerns derived from these efforts suggests that three major hurdles loom in front of using xenobiotic metabolism databases more effectively in the future. These hurdles include: the need for an improved treatment of chemical structure in three-dimensions (3D); a better quantitative accounting of competitive and complementary biotransformation pathways; and, the critical need for a comprehensive, human drug metabolism database (hDMdb) that can serve as a bio/chemoinformatic resource pertaining to drug metabolism and drug metabolism-related drug-drug interactions in general. Approaches that might be taken to traverse each of these hurdles are discussed herein where: the first involves maturation of chemical structures from simple 2D entries into more sophisticated 3D displays that can also account for interactions with relevant biological surfaces; the second involves a systematic, pair-wise comparison of various metabolic options in a statistically driven manner relative to chemical structure descriptors; and, the third involves mounting a hDMdb on the Internet in a user-friendly manner that it is available via a non-profit format.
Erhardt
Paul W
PW
Center for Drug Design and Development, The University of Toledo College of Pharmacy, USA. paul.erhardt@utoledo.edu
D016208:Databases, Factual; D004347:Drug Interactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D011237:Predictive Value of Tests; D013329:Structure-Activity Relationship; D015262:Xenobiotics / Q000378:metabolism
D004364:Pharmaceutical Preparations; D015262:Xenobiotics