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OCT1-dependent uptake of structurally diverse pyrrolizidine alkaloids in human liver cells is crucial for their genotoxic and cytotoxic effects
Pyrrolizidine alkaloids (PAs) are important plant hepatotoxins, which occur as contaminants in plant-based foods, feeds and phytomedicines. Numerous...
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Using the LeiCNS-PK3.0 Physiologically-Based Pharmacokinetic Model to Predict Brain Extracellular Fluid Pharmacokinetics in Mice
IntroductionThe unbound brain extracelullar fluid (brain ECF ) to plasma steady state partition coefficient, K p,uu,BBB , values provide steady-state...
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The effects of pro-inflammatory cytokines and glutamate on l-arginine transport in a human microglial cell line (HMC-3)
PurposeNeuroinflammation and microglial activation are the key factors in neurodegenerative motor neuron diseases. Microglial activation has been...
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Analysis of Non-linear Pharmacokinetics of P-Glycoprotein Substrates in a Microfluidic Device Using a Mathematical Model that Includes an Unstirred Water Layer (UWL) Compartment
PurposeThe purpose of this research is to analyze non-linear pharmacokinetics of P-glycoprotein (P-gp) substrates in a cell based assay of a...
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Study of the roles of cytochrome P450 (CYPs) in the metabolism and cytotoxicity of perhexiline
Perhexiline is a prophylactic antianginal agent developed in the 1970s. Although, therapeutically, it remained a success, the concerns of its severe...
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Hyperglycaemia-induced impairment of the autorhythmicity and gap junction activity of mouse embryonic stem cell-derived cardiomyocyte-like cells
Diabetes mellitus with hyperglycaemia is a major risk factor for malignant cardiac dysrhythmias. However, the underlying mechanisms remain unclear,...
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Quinidine
Cinchona bark is an ancient herb with magic medical effects. Quinidine is one of the alkaloids in the cinchona bark, also known as the isomer of...
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Automatic Newton Modeling in Clinical Pharmacology (15 Alfentanil Dosages, 15 Quinidine Time-Concentration Relationships)
Traditional regression analysis selects a mathematical function, and, then, uses the data to find the best fit parameters. For example, the...
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Emotional and Neuropsychiatric Disorders Associated with Alzheimer’s Disease
Alzheimer’s disease is associated with impairments in emotional communication including comprehension and production of facial emotional expressions,...
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Differences in P-glycoprotein activity in human and rodent blood–brain barrier assessed by mechanistic modelling
Variation in the efficacy and safety of central nervous system drugs between humans and rodents can be explained by physiological differences between...
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Considerations and Caveats when Applying Global Sensitivity Analysis Methods to Physiologically Based Pharmacokinetic Models
Three global sensitivity analysis (GSA) methods (Morris, Sobol and extended Sobol) are applied to a minimal physiologically based PK (mPBPK) model...
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The Use of Microdosing for In vivo Phenoty** of Cytochrome P450 Enzymes: Where Do We Stand? A Narrative Review
Cytochrome P450 (CYP) enzymes play a central role in the elimination of approximately 80% of all clinically used drugs. Differences in CYP enzyme...
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Improvement of Workflows and Assay Reproducibility by The Introduction of “Assay-Ready” Culturing of MDCK Cells for Transport Studies
ObjectiveIn previous studies, we established and validated three Madin Darby Canine Kidney MDCKII cell lines, recombinantly modified with zinc finger...
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Drugs Acting on Renal and Cardiovascular Function
Cardiovascular medications play a crucial role in medical practice by influencing the functionality of the heart and blood vessels. These medications...
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The Short QT Syndrome
The short QT syndrome (SQTS) is characterised by abbreviated QT intervals on the electrocardiogram and by an increased risk of atrial and ventricular...
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N-oxidation Regioselectivity and Risk Prediction Using DFT-ALIE Calculations
IntroductionThe formation of N -oxide degradants is a major concern in development of new drugs due to potential effects on a compound’s...
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A clinical pharmacokinetic drug-drug interaction study between dextromethorphan and emvododstat, a potent anti-SARS-CoV-2 dihydroorotate dehydrogenase inhibitor
PurposeA therapeutic agent that targets both viral replication and the hyper-reactive immune response would offer a highly desirable treatment for...
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Early Treatment with Quinidine in 2 Patients with Epilepsy of Infancy with Migrating Focal Seizures (EIMFS) Due to Gain-of-Function KCNT1 Mutations: Functional Studies, Clinical Responses, and Critical Issues for Personalized Therapy
Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare early-onset developmental epileptic encephalopathy resistant to anti-epileptic...
