Multispecies Machine Learning Predictions of In Vitro Intrinsic Clearance with Uncertainty Quantification Analyses.
Sign Up to like & getrecommendations! Published in 2022 at "Molecular pharmaceutics"
DOI: 10.1021/acs.molpharmaceut.2c00680
Abstract: In pharmaceutical research, compounds are optimized for metabolic stability to avoid a too fast elimination of the drug. Intrinsic clearance (CLint) measured in liver microsomes or hepatocytes is an important parameter during lead optimization. In… read more here.
Keywords: uncertainty; machine learning; intrinsic clearance; clint ... See more keywords
Identification of UGTs and BCRP as potential pharmacokinetic determinants of the natural flavonoid alpinetin
Sign Up to like & getrecommendations! Published in 2019 at "Xenobiotica"
DOI: 10.1080/00498254.2018.1440657
Abstract: Abstract Alpinetin is a natural flavonoid showing a variety of pharmacological effects such as anti-inflammatory, anti-tumor and hypolipidemic activities. Here, we aim to determine the roles of UDP-glucuronosyltransferases (UGTs) and breast cancer resistance protein (BCRP)… read more here.
Keywords: glucuronidation; min nmol; alpinetin; activity ... See more keywords
Evaluation of the Disconnect between Hepatocyte and Microsome Intrinsic Clearance and In Vitro In Vivo Extrapolation Performance
Sign Up to like & getrecommendations! Published in 2020 at "Drug Metabolism and Disposition"
DOI: 10.1124/dmd.120.000131
Abstract: The use of in vitro in vivo extrapolation (IVIVE) from human hepatocyte (HH) and human liver microsome (HLM) stability assays is a widely accepted predictive methodology for human metabolic clearance (CLmet). However, a systematic underprediction… read more here.
Keywords: vitro vivo; hlm; clearance; vivo extrapolation ... See more keywords
Exploring the Pharmacokinetic Mysteries of the Liver: Application of Series Compartment Models of Hepatic Elimination
Sign Up to like & getrecommendations! Published in 2023 at "Drug Metabolism and Disposition"
DOI: 10.1124/dmd.122.001190
Abstract: Among the basic hepatic clearance models, the dispersion model (DM) is the most physiologically sound compared with the well-stirred model and the parallel tube model. However, its application in physiologically-based pharmacokinetic (PBPK) modeling has been… read more here.
Keywords: hepatic elimination; clint; scm; compartment models ... See more keywords
A Novel Method for Predicting the Human Inherent Clearance and Its Application in the Study of the Pharmacokinetics and Drug–Drug Interaction between Azidothymidine and Fluconazole Mediated by UGT Enzyme
Sign Up to like & getrecommendations! Published in 2021 at "Pharmaceutics"
DOI: 10.3390/pharmaceutics13101734
Abstract: In order to improve the benefit–risk ratio of pharmacokinetic (PK) research in the early development of new drugs, in silico and in vitro methods were constructed and improved. Models of intrinsic clearance rate (CLint) were… read more here.
Keywords: drug interaction; drug drug; method; drug ... See more keywords