Title:Development and Uses of Offline and Web-Searchable Metabolism Databases - The Case of Benzo[a]pyrene
Volume: 19
Issue: 1
Author(s): Slobodan P. Rendic*Frederick P. Guengerich
Affiliation:
- Haulikova 6, Zagreb,Croatia
Keywords:
P450, CYP, transporters, metabolism databases, web-database, benzo[a]pyrene, metabolic activation, xenobiotics, endobiotics.
Abstract: Background: The present work describes development of offline and web-searchable metabolism databases
for drugs, other chemicals, and physiological compounds using human and model species, prompted by the
large amount of data published after year 1990. The intent was to provide a rapid and accurate approach to published
data to be applied both in science and to assist therapy.
Methods: Searches for the data were done using the Pub Med database, accessing the Medline database of references
and abstracts. In addition, data presented at scientific conferences (e.g., ISSX conferences) are included covering the
publishing period beginning with the year 1976.
Results: Application of the data is illustrated by the properties of benzo[a]pyrene (B[a]P) and its metabolites. Analysis
show higher activity of P450 1A1 for activation of the (-)- isomer of trans-B[a]P-7,8-diol, while P4501B1 exerts
higher activity for the (+)- isomer. P450 1A2 showed equally low activity in the metabolic activation of both isomers.
Conclusion: The information collected in the databases is applicable in prediction of metabolic drug-drug and/or
drug-chemical interactions in clinical and environmental studies. The data on the metabolism of searched compound
(exemplified by benzo[a]pyrene and its metabolites) also indicate toxicological properties of the products of specific
reactions. The offline and web-searchable databases had wide range of applications (e.g. computer assisted drug
design and development, optimization of clinical therapy, toxicological applications) and adjustment in everyday life
styles.
