Ghafourian-BE-11Oct-Biliary.pdf (2.35 MB)
Estimation of biliary excretion of foreign compounds using properties of molecular structure
journal contribution
posted on 2023-06-09, 03:25 authored by Mohsen Sharifi, Taravat GhafourianBiliary excretion is one of the main elimination pathways for drugs and/or their metabolites. Therefore, an insight into the structural profile of cholephilic compounds through accurate modelling of the biliary excretion is important for the estimation of clinical pharmacokinetics in early stages of drug discovery. The aim of this study was to develop quantitative structure-activity relationships as computational tools for the estimation of biliary excretion and identification of the molecular properties controlling this process. The study used percentage of dose excreted intact into bile measured in vivo in rat for a diverse dataset of 217 compounds. Statistical techniques were multiple linear regression analysis, regression trees, random forest and boosted trees. A simple regression tree model generated using the CART algorithm was the most accurate in the estimation of the percentage of bile excretion of compounds, and this outperformed the more sophisticated boosted trees and random forest techniques. Analysis of the outliers indicated that the models perform best when lipophilicity is not too extreme (log P?
History
Publication status
- Published
File Version
- Accepted version
Journal
AAPS JournalISSN
1550-7416Publisher
Springer VerlagExternal DOI
Issue
1Volume
16Page range
65-78Department affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-12-01First Open Access (FOA) Date
2017-12-01First Compliant Deposit (FCD) Date
2017-12-01Usage metrics
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No categories selectedKeywords
analgesic agent; anti human immunodeficiency virus agent; antineoplastic agent; cephalosporin derivative; dye; folic acid; hydroxymethylglutaryl coenzyme A reductase inhibitor; macrolide; nonsteroid antiinflammatory agent; penicillin derivative; quaternary ammonium derivative; quinoline derived antiinfective agent; sulfanilamide; thrombin inhibitorarticle; biliary excretion; drug excretion; hydrophilicity; in vivo study; linear regression analysis; lipophilicity; mathematical model; nonhuman; prediction; process development; quantitative structure activity relation; random forest; structure analysis; validation processGallbladder; Liver; ModelsChemical; Pharmacokinetics; Regression Analysis; Structure-Activity Relationship
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