Weakly basic compounds propose biopharmaceutics risks due to the possibility of precipitation out of solution when passing from the stomach to the intestine.
Considerations for Physiologically Based Modeling in Liver Disease: From Nonalcoholic Fatty Liver (NAFL) to Nonalcoholic Steatohepatitis (NASH)
Nonalcoholic fatty liver disease (NAFLD), representing a clinical spectrum ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) is rapidly...
Chemical Reactivity and Optical and Pharmacokinetics Studies of 14 Multikinase Inhibitors and Their Docking Interactions Toward ACK1 for Precision Oncology
Activated Cdc42-associated kinase 1 (ACK1/TNK2) has a significant role in cell endocytosis, survival, proliferation, and migration.
Structure-based 3D-Pharmacophore modeling to discover novel interleukin 6 inhibitors: An in silico screening, molecular dynamics simulations and binding free energy calculations
Interleukin 6 (IL-6) is a cytokine with various biological functions in immune regulation, hematopoiesis, and inflammation.
A model-based approach to bridging plasma and dried blood spot concentration data for phase 3 verubecestat trials
In-clinic venous dried blood spot (DBS) pharmacokinetic (PK) sampling was incorporated into two phase 3 studies of verubecestat for
Physiologically Based Biopharmaceutics Model of Vildagliptin Modified Release (MR) Tablets to Predict In Vivo Performance and Establish Clinically Relevant Dissolution Specifications
The objective of the study was to predict pharmacokinetic (PK) and pharmacodynamic (PD) parameters of matrix-based modified release (MR) drug product of vildagliptin.
Sputum lipoarabinomannan (LAM) as a biomarker to determine sputum mycobacterial load: exploratory and model-based analyses of integrated data from four cohorts
Despite the high global disease burden of tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb) infection, novel treatments remain an urgent medical need. Development efforts continue to
Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods
Background: Inflammation is a critical component of many disease progressions, such as malignancy, cardiovascular and rheumatic diseases.
PBK modelling of topical application and characterisation of the uncertainty of Cmax estimate: A case study approach
Combined with in vitro bioactivity data, physiologically based kinetic (PBK) models has increasing applications in next generation risk assessment for animal-free safety...
An IQ Consortium Perspective on Connecting Dissolution Methods to In Vivo Performance: Analysis of an Industrial Database and Case Studies to Propose a Workflow
Assessment of bioperformance to inform formulation selection and development decisions is an important aspect of drug development.
PBK modelling of topical application and characterisation of the uncertainty of Cmax estimate: A case study approach
Combined with in vitro bioactivity data, physiologically based kinetic (PBK) models has increasing applications in next generation risk assessment for animal-free safety decision...
Identification and characterization of urapidil stress degradation products by LC-Q-TOF-MS and NMR: Toxicity prediction of degradation products
Urapidil, an antihypertensive drug is subjected to various stress conditions (acidic, basic, neutral, oxidative and photolytic) as per ICH guidelines.
Prediction of tissue and urine concentrations of 2-phenoxyethanol and its metabolite 2-phenoxyacetic acid in rat and human after oral and dermal exposures via GastroPlus™ physiologically based pharmacokinetic modelling
A physiologically based pharmacokinetic (PBPK) model for the important chemical phenoxyethanol (PhE) and its metabolite phenoxyacetic acid (PhAA) was built via GastroPlusTM...
Exploration of the Plausible Mechanism of Ethambutol Induced Ocular Toxicity by Using Proteomics Informed Physiologically Based Pharmacokinetic (PBPK) Modeling
Ethambutol (EMB) is a first-line anti-tubercular drug that is known to cause optic neuropathy.
Use In Silico and In Vitro Methods to Screen Hepatotoxic Chemicals and CYP450 Enzyme Inhibitors
In silico and in vitro methods have emerged as valuable tools to rapidly screen and prioritize large numbers of chemicals including new drug entities, food ingredients, and environmental compounds for further in vivo analysis.
Model-based meta-analysis of relapsing mouse model studies from the critical path to tuberculosis drug regimens initiative database
erculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb), remains a leading infectious disease-related cause of death worldwide, necessitating the development of new
Molecular docking and pharmacokinetics studies of Curcuma longa (Curcumin) potency against Ebola virus
The Ebola virus disease causing hemorrhagic fever in human, has been known for nearly about 40 years, with the most recent outbreak being in West Africa creating...
Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria
A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay.
High-Throughput Screening for Extracellular Inhibitors of the FLT3 Receptor Tyrosine Kinase Reveals Chemically Diverse and Druggable Negative Allosteric Modulators
Inhibiting receptor tyrosine kinases is commonly achieved by two main strategies targeting either the intracellular kinase domain by low molecular weight compounds or...
In vivo neurophysiological assessment of in silico predictions of neurotoxicity: Citronellal, 3,4-dichloro-1-butene, and benzyl bromoacetate
Neurotoxicants may be widespread in the environment and can produce serious health impacts in the human population.