Data Curation can Improve the Prediction Accuracy of Metabolic Intrinsic Clearance [PDF]
Molecular Informatics, 2019 AbstractA key consideration at the screening stages of drug discovery is in vitro metabolic stability, often measured in human liver microsomes. Computational prediction models can be built using a large quantity of experimental data available from public databases, but these databases typically contain data measured using various protocols in ...
Tsuyoshi Esaki +2 more
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Predicting Intrinsic Clearance for Drugs and Drug Candidates Metabolized by Aldehyde Oxidase [PDF]
Molecular Pharmaceutics, 2013 Metabolism by aldehyde oxidase (AO) has been responsible for a number of drug failures in clinical trials. The main reason is the clearance values for drugs metabolized by AO are underestimated by allometric scaling from preclinical species. Furthermore, in vitro human data also underestimates clearance.
Jeffrey P Jones
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Beyond the Michaelis–Menten: Evaluation of a tQSSA‐Based IVIVE Approach for Predicting In Vivo Intrinsic Clearance From Hepatocyte Assays [PDF]
CPT: Pharmacometrics & Systems PharmacologyThe classical Michaelis–Menten model, under the standard quasi‐steady‐state approximation (sQSSA), is widely used in in vitro‐in vivo extrapolation (IVIVE) studies using hepatocyte or human liver microsomal (HLM) assays to predict intrinsic hepatic ...
Ngoc‐Anh Thi Vu +6 more
doaj +2 more sources
Interlaboratory Variability in Human Hepatocyte Intrinsic Clearance Values and Trends with Physicochemical Properties. [PDF]
Pharm Res, 2019 To examine the interlaboratory variability in CLint values generated with human hepatocytes and determine trends in variability and clearance prediction accuracy using physicochemical and pharmacokinetic parameters.Data for 50 compounds from 14 papers were compiled with physicochemical and pharmacokinetic parameter values taken from various sources ...
Bowman CM, Benet LZ.
europepmc +6 more sources
Environment International, 2020 The renal and hepatic clearance rates of organophosphate esters (OPEs) in humans were estimated. Six OPEs and their corresponding diester metabolites (mOPEs) were quantified respectively in 30 paired human plasma and urine samples collected in Hengshui ...
Wenjue Zhong, Qing Liu, Lingyan Zhu
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Effect of Cytochrome P450 2C9 genetic polymorphism on agomelatine metabolism in vitro [PDF]
PeerJBackground Genetic polymorphisms of CYP2C9 significantly influence the efficacy and safety of some drugs, which potentially lead to adverse effects and therapeutic failure.
Ping Fang +10 more
doaj +3 more sources
Evaluation and comparison of in vitro intrinsic clearance rates measured using cryopreserved hepatocytes from humans, rats, and rainbow trout [PDF]
Toxicology, 2021 Kellie Fay, Scott Lynn, John Nichols
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Reliability of In Vitro Methods Used to Measure Intrinsic Clearance of Hydrophobic Organic Chemicals by Rainbow Trout: Results of an International Ring Trial [PDF]
Toxicological Sciences, 2018 Christian Schlechtriem +2 more
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Molecules, 2023 Sapitinib (AZD8931, SPT) is a tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) family (pan-erbB). In multiple tumor cell lines, STP has been shown to be a much more potent inhibitor of EGF-driven cellular proliferation than ...
Mohamed W. Attwa +3 more
doaj +1 more source
Effects of CYP2C19 variants on the metabolism of tapentadol in vitro [PDF]
Iranian Journal of Basic Medical Sciences, 2022 Objective(s): This study aims to evaluate the catalytic activities of 31 CYP2C19 alleles and their effects on the metabolism of tapentadol in vitro. Materials and Methods: Insect microsomes expressing the CYP2C19 alleles were incubated with 50–1250 μM ...
Ren-ai Xu +5 more
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