Elevations of liver enzymes have been observed in clinical trials with BAL30072, a novel antibiotic. In vitro assays have identified potential mechanisms for the observed hepatotoxicity, including...
Evaluation and Optimization of Pharmacokinetic Models for in Vitro to in Vivo Extrapolation of Estrogenic Activity for Environmental Chemicals
To effectively incorporate in vitro data into regulatory use, confidence must be established in the quantitative extrapolation of in vitro activity to relevant end...
Preclinical models for colonic absorption, application to controlled release formulation development
Oral controlled release (CR) formulations have many benefits and have become a valuable resource for the local and systemic administration of drugs.
Discussions on the hepatic well-stirred model: Re-derivation from the dispersion model and re-analysis of the lidocaine data
Roberts and Rowland explained the well-stirred model as an extreme case of the dispersion model when the dispersion number is infinity.
Characterization of solution stress degradation products of aliskiren and prediction of their physicochemical and ADMET properties
Forced degradation studies on aliskiren were carried out according to ICH and WHO guidelines. Six degradation products were formed in total in the solution state.
A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates
Misuse of prescription opioids, opioid addiction, and overdose underscore the urgent need for developing addiction-free effective medications for treating severe pain.
Retention characteristics of some antibiotic and anti-retroviral compounds in hydrophilic interaction chromatography using isocratic elution, and gradient elution with repeatable partial equilibration
The separation of some zwitterionic, basic and neutral antibiotic and antiretroviral compounds was studied using hydrophilic interaction chromatography (HILIC) on bare silica, bonded amide and urea superficially porous phases.
Physiological Considerations and In Vitro Strategies for Evaluating the Influence of Food on Drug Release from Extended-Release Formulations
Food effects on oral drug bioavailability are a consequence of the complex interplay between drug, formulation and human gastrointestinal (GI) physiology.
Applications of Clinically Relevant Dissolution Testing: Workshop Summary Report
This publication summarizes the proceedings of day 3 of a 3-day workshop on “Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development.”
Amino acid conjugated chitosan nanoparticles for the brain targeting of a model dipeptidyl peptidase-4 inhibitor
Saxagliptin (SAX) is a dipeptidyl peptidase-4 enzyme inhibitor molecule now explored for its activity in the therapy of Alzheimer’s disease.
Impact of Drug Physicochemical Properties on Lipolysis-triggered Drug Supersaturation and Precipitation from Lipid-Based Formulations
In this study we investigated lipolysis-triggered supersaturation and precipitation of a set of model compounds formulated in lipid-based formulations (LBFs).
Applications of Multi-Class Machine Learning Models to Drug Design
Until recently, machine learning classification models in Cheminformatics literature have generally modeled binary endpoints (active/inactive, substrate/non-substrate, toxic/non-toxic, etc.)
Assessing the potential of solid dispersions to improve dissolution rate and bioavailability of valsartan: In vitro-in silico approach
This study aimed to improve dissolution rate of valsartan in an acidic environment and consequently its oral bioavailability by solid dispersion formulation.
Using DILIsym, A Quantitative Systems Toxicology (QST) Software Tool of Drug-Induced Liver Injury (DILI), To Assess DILI Risk in Drug Development
A combination of multiple mechanistic, in silico modeling approaches can facilitate drug discovery (QSAR, PBPK, QSP and QST).
Modeling Enterohepatic Circulation (EHC) in GastroPlus®
This video shows how to set up enterohepatic circulation of ezetimibe in order to accurately simulate the in vivo plasma protein concentration.
Introducing a computational method to estimate and prioritize systemic body exposure of organic chemicals in humans using their physicochemical properties
This report describes a computational method developed to predict systemic exposure (s-exposure), chemical disposition {(CD) intestinal absorption, transport, membrane permeability, distribution...
Identification of chemically diverse GABAA agonists as potential anti-epileptic agents using structure-guided virtual screening, ADMET, quantum mechanics and clinical validation through off-target analysis
Development of resistance against existing anti-epileptic drugs has alarmed the scientific innovators to find novel potential chemical starting points for the treatment of epilepsy and GABAA inhibition is a promising...
Design, Synthesis and Pharmacology of Aortic-Selective Acyl-CoA: Cholesterol O-Acyltransferase (ACAT/SOAT) Inhibitors
We describe our molecular design of aortic-selective acyl-coenzyme A:cholesterol O-acyltransferase (ACAT, also abbreviated as SOAT) inhibitors, their structure-activity relationships (SARs) and their…
Exploration of Carboxy pyrazole derivatives: Synthesis, alkaline Phosphatase, nucleotide pyrophosphatase/phosphodiesterase and nucleoside triphosphate diphosphohydrolase inhibition studies with potential anticancer profile
In the present work we report the synthesis of new aryl pyrazole derivatives using 1,3-dicarbonyl motifs.
Synthesis of Proline Derived Benzenesulfonamides: A Potent Anti-Trypanosoma Brucei Gambiense Agent
Thousands of death in Africa and other developing nations are still attributed to trypanosomiasis. Excessive sleep has been associated with increased inflammation. We report herein, the synthesis…