Solubility, dissolution, and precipitation in the gastrointestinal tract can be critical for the oral bioavailability of weakly basic drugs.
Application of a Dynamic Fluid & pH Model to Simulate Intraluminal and Systemic Concentrations of a Weak Base in GastroPlus™
The application of preclinical in vitro and in silico models can help formulation scientists to predict the in vivo performance of a drug in an early stage of oral drug product development.
In Silico Simulation of Dissolution Profiles for Development of Extended-Release Doxazosin Tablets
Developing extended-release (ER) formulations with appropriate release characteristics can be challenging for formulation scientists.
Can Bile Salt Export Pump Inhibition Testing in Drug Discovery and Development Reduce Liver Injury Risk? An International Transporter Consortium Perspective
Bile salt export pump (BSEP) inhibition has emerged as an important mechanism that may contribute to the initiation of human drug-induced liver injury (DILI).
Molecular Drivers of Crystallization Kinetics for Drugs in Supersaturated Aqueous Solutions
In this study, we explore molecular properties of importance in solution-mediated crystallization occurring in supersaturated aqueous drug solutions.
Using Quantitative Systems Toxicology to Investigate Observed Species Differences in CKA-Mediated Hepatotoxicity
CKA, a chemokine receptor antagonist intended for treating inflammatory conditions, produced dose-dependent hepatotoxicity in rats but advanced into the clinic where single doses of CKA up to 600 mg appeared safe in humans.
Drug discovery and computational strategies in the multitarget drugs era
The pharmaceutical industry is increasingly joining chemoinformatics in the search for the development of new drugs to be used in the treatment of diseases.
Nonclinical pharmacokinetics and in vitro metabolism of H3B-6545, a novel selective ERα covalent antagonist (SERCA)
H3B-6545, a novel selective estrogen receptor (ER)α covalent antagonist (SERCA) which inactivates both wild-type and mutant ERα, is in clinical development for the treatment of metastatic breast cancer.
Second generation of diazachrysenes: Protection of Ebola virus infected mice and mechanism of action
Ebola virus (EBOV) causes a deadly hemorrhagic fever in humans and non-human primates.
Synthesis, Molecular Docking, and Antimycotic Evaluation of Some 3-Acyl Imidazo[1,2-a]pyrimidines
A series of 3-benzoyl imidazo[1,2-a]pyrimidines, obtained from N-heteroarylformamidines in good yields, was tested in silico and in vitro for binding and inhibition of seven Candida species...
Application of in silico Tools in Clinical Practice using Ketoconazole as a Model Drug
Hypochlorhydria is a condition where the production of hydrochloric acid in the stomach is decreased. As a result, the intragastric pH is elevated.
Prediction of ARA/PPI Drug-Drug Interactions at the Drug Discovery and Development Interface
Advances in understanding of human disease has prompted the Food and Drug Administration to classify certain molecules as “break-through therapies”, providing an accelerated review...
ETCM: an encyclopaedia of traditional Chinese medicine
Traditional Chinese medicine (TCM) is not only an effective solution for primary health care, but also a great resource for drug innovation and discovery.
Data Standards for Model-Informed Drug Development: an ISoP Initiative
Analysis datasets are fundamental components of pharmacometric analyses and their quality and readiness highly correlate with
Evaluation of Potential Carcinogenicity of Organic Chemicals in Synthetic Turf Crumb Rubber
Currently, there are >11,000 synthetic turf athletic fields in the United States and >13,000 in Europe. Concerns have been raised about exposure to carcinogenic chemicals resulting from...
Population pharmacokinetics and exposure – safety analyses of nivolumab in patients with relapsed or refractory classical hodgkin lymphoma
Nivolumab, a fully human immunoglobulin G4 monoclonal anti-programmed death-1 antibody, has demonstrated clinical benefits in multiple tumors, including classical Hodgkin lymphoma.
Machine Learning: What, Why, and How?
Since the beginning of computers era, an enormous amount of data generated seems to be ever-increasing and could be of great use with efficient learning techniques.
Tannic Acid Solution: A Better Fixative Solution Than Formalin for Elastin and Collagen—Toxic and Morphological Assessment.
Formaldehyde is commonly used worldwide, even though it is classified as carcinogenic to humans by the International Agency for Research on Cancer.
Design, synthesis, structural characterization and in vitro evaluation of new 1,4-disubstituted-1,2,3-triazole derivatives against glioblastoma cells
A new series of 1,4-disubstituted-1,2,3-triazole derivatives were synthesized through the copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (Click chemistry) and their inhibitory activities were...
The Irrelevance of in vitro Dissolution in Setting Product Specifications for Drugs like Dextromethorphan that are Subject to Lysosomal Trapping
The purpose of the current study was to develop a physiologically-based pharmacokinetic (PBPK) model for dextromethorphan (DEX) and its metabolites in extensive (EM) and poor metabolizers (PM).