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).
Activation of CD8+ T Cells in the Context of Amodiaquine-Induced Liver Injury Advances Groundwork for Mathematical Representation of Idiosyncratic Drug-Induced Liver Injury (iDILI)
Extensive progress has been made in identifying mechanisms for dose-dependent drug-induced liver injury (DILI) and in developing screening assays to reduce its incidence.
Assessing Effects of BHV-0223 40 mg Zydis® Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym®
To quantitatively and mechanistically compare the liver toxicity potential of oral riluzole versus BHV-0223, combining clinical and mechanistic data, using DILIsym.
A Model-Based Approach to Bridging Plasma and Dried Blood Spot Concentration Data for Phase 3 Verubecestat Trials
Dried blood spot (DBS) pharmacokinetic (PK) sampling was investigated as a potential alternative to plasma sampling for Phase 3 verubecestat (MK-8931) trials due to several potential advantages (ie, reduced cost, reduced clinical site burden, and lower blood volume requirements)
Development of a Physiologically Based Pharmacokinetic Model for Losartan and Its Active Metabolite E3174 – Ethnic Differences in Pharmacokinetics between Caucasian and Asian Populations
Losartan is a selective, competitive angiotensin 11 receptor type 1 (AT1) antagonist for hypertension treatment.
Quantitative Systems Toxicology Modeling Using DILIsym Suggests That Mitochondrial Biogenesis Could Explain Adaptation to Drug-Induced Liver Injury (DILI)
Resolution of elevations of the liver injury biomarker serum ALT despite continued drug dosing, termed “adaptation”, is commonly observed in clinical trials, but the underlying mechanisms behind this phenomenon remain unclear.
Representation of Crizotinib and Pazopanib-mediated Drug-Induced Liver Injury (DILI) Using Quantitative Systems Toxicology (QST)
Crizotinib and pazopanib are oral receptor tyrosine kinase inhibitors (TKIs).
Concentration-QT Analysis of Quizartinib in Patients With Relapsed/Refractory AML
FMS-like tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells, and signaling through FLT3 promotes these cells’ proliferation and differentiation.
Zonal Extracellular Matrix (ECM) Accumulation in Nonalcoholic Steatohepatitis (NASH) Characterized by a Mathematical Model of Fibrosis
Non-alcoholic fatty liver disease (NAFLD) is of growing concern, within developed countries, with recent estimates suggesting up to, 30% of the US population may be affected.
New Approach Methods for Testing Chemicals for Endocrine Disruption Potential
Concern that chemicals in the environment can disrupt the endocrine systems of humans and ecological species (fish, frogs, birds) has driven the development of bioassays to test for endocrine activity.
Preparation of lapatinib ditosylate solid dispersions using solvent rotary evaporation and hot melt extrusion for solubility and dissolution enhancement
The objective of this study was to enhance solubility and dissolution of lapatinib (LB) ditosylate (DT) using solid dispersions (SD) prepared by solvent rotary evaporation (SRE) and hot melt extrusion (HME).
Bioformulative concepts on intracellular organ specific bioavailability
Bioavailability is an ancient but effective terminology by which the entire therapeutic efficacy of a drug directly or indirectly relays.
Role of Physiologically Based Kinetic modelling in addressing environmental chemical mixtures – a review
The role of Physiologically Based Kinetic (PBK) modelling in assessing mixture toxicology has been growing for the last three decades. It has been widely used to investigate and address interactions in mixtures.
Quantitative prediction of oral bioavailability of a lipophilic antineoplastic drug bexarotene administered in lipidic formulation using a combined in vitro lipolysis/microsomal metabolism approach
For performance assessment of the lipid-based drug delivery systems (LBDDS), in vitrolipolysis is commonly applied because traditional dissolution tests do not reflect the complicated in vivo micellar formation and solubilisation processes.
Model-based drug development in pulmonary delivery: Pharmacokinetic analysis of novel drug candidates for treatment of Pseudomonas aeruginosa lung infection
Antibiotic resistance is a major public health threat worldwide. In particular, about 80% of cystic fibrosis patients have chronic Pseudomonas aeruginosa (PA) lung infection resistant to many current antibiotics.
Estimating Predictive Uncertainty for Ensemble Regression Models by Gamma Error Analysis
The Standard Error (SE) of Prediction: a Measure of Individual Uncertainties
Galactosylated chitosan Triptolide nanoparticles for overcoming hepatocellular carcinoma: Enhanced therapeutic efficacy, low toxicity, and validated network regulatory mechanisms
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. Current therapies present significant limitations.
Dibutyltin(IV) Complexes Derived from L-DOPA: Synthesis, Molecular Docking, Cytotoxic and Antifungal Activity
A series of organotin(IV) complexes was herein prepared and characterized. A one-pot synthetic strategy afforded reasonable to high yields, depending on the nature of the ligand.
Bringing physiologically-based pharmacokinetic (PBPK) simulation to early drug discovery and development
Lack of efficacy continues to be a problem in drug development. Piecemeal rules of thumb such as Lipinski’s Rule of Five [1] help avoid compounds likely to be poorly...