Data Curation can Improve the Prediction Accuracy of Metabolic Intrinsic Clearance. [PDF]
Mol Inform, 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 ...
Esaki T +6 more
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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.
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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
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Predicting intrinsic clearance for drugs and drug candidates metabolized by aldehyde oxidase. [PDF]
Mol Pharm, 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.
Jones JP, Korzekwa KR.
europepmc +5 more sources
Evaluation of the Use of a Medium Cut‐Off Dialyser Theranova 400 for Severe Metaldehyde Intoxication in Three Dogs: Dialytic Clearance and Therapeutic Response [PDF]
Veterinary Medicine and ScienceObjective To describe the clinical utility and toxin removal kinetics of a commercially available medium cut‐off (MCO) haemodialyser as emergent treatment of severe metaldehyde intoxication in three dogs.
Maxime Rodary +5 more
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Intrinsic mechanical vibrations as a missing dimension in amyloid-β clearance: a mechanochemical hypothesis for Alzheimer’s disease [PDF]
Frontiers in Aging NeuroscienceAlzheimer’s disease is widely viewed as a disorder of disturbed amyloid-β (Aβ) homeostasis, yet it remains unclear why Aβ shifts from routine turnover to progressive retention and plaque growth in mid-life.
Xiaochen Lai
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Pharmaceutics, 2023 Alectinib, also known as Alecensa®, is prescribed for the therapeutic treatment of individuals diagnosed with metastatic non-small cell lung cancer (NSCLC) who have a specific genetic mutation referred to as anaplastic lymphoma kinase (ALK) positivity ...
Mohamed W. Attwa +3 more
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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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Molecules, 2023 Selpercatinib (SLP; brand name Retevmo®) is a selective and potent RE arranged during transfection (RET) inhibitor. On 21 September 2022, the FDA granted regular approval to SLP (Retevmo, Eli Lilly, and Company).
Mohamed W. Attwa +4 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
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