Metabolite Assignment Considerations & Caveats: One compound can (and often does) give rise to two or more mass spectral (MS) peaks - but there should only be one HPLC peak per compound...
![Species differences in metabolism of a new antiepileptic drug candidate, DSP‐0565 [2‐(2’‐fluoro[1,1’‐biphenyl]‐2‐yl)acetamide]](https://www.simulations-plus.com/wp-content/themes/simulations-plus/library/dist/img/default_square-large.jpg)
Species differences in metabolism of a new antiepileptic drug candidate, DSP‐0565 [2‐(2’‐fluoro[1,1’‐biphenyl]‐2‐yl)acetamide]
The metabolism and pharmacokinetics of DSP‐0565 [2‐(2'‐fluoro[1,1'‐biphenyl]‐2‐yl)acetamide], an antiepileptic drug candidate, was investigated in rats, dogs, and humans. In human hepatocytes, [14C]DSP‐0565 was primarily metabolized via amide bond hydrolysis to (2'‐fluoro[1,1'‐biphenyl]‐2‐yl)acetic acid (M8), while in rat and dog hepatocytes...
Cardiac glycoside Cerberin exerts anticancer activity through PI3K/AKT/mTOR signal transduction inhibition
Natural products possess a significant role in anticancer therapy and many currently-used anticancer drugs are of natural origin.
Clarity in Reporting Parameter Variance Needed to Improve Use of Published Models for Simulation Applications
Since published pharmacokinetic and pharmacodynamic models are often used by others for the purpose of simulations, enhanced clarity in reporting and clear statements regarding assumptions will improve the reproducibility of...
ADMET Predictor® 9.5 Webinar
Significant enhancements have been made throughout both ADMET Predictor and MedChem Designer™.
Prediction of ticagrelor and its active metabolite in liver cirrhosis populations using a physiologically based pharmacokinetic model involving pharmacodynamics
Ticagrelor, a P2Y12 receptor antagonist, has been highly recommended for use in acute coronary syndrome (ACS).
Evaluation of Food Effect on the Oral Absorption of Clarithromycin from Immediate Release Tablet using Physiological Modelling
The aim of the present study was to investigate the influence of food on the oral absorption of Clarithromycin by evaluating the effect of media parameters such as; pH, bile secretions and food composition on...
A physiologically based pharmacokinetic (PBPK) modeling of amlodipine: High enterocyte binding, not enterohepatic circulation, is responsible for the long Tmax
Amlodipine is a second generation calcium channel blocker that has been widely used in the therapy of hypertension and angina pectoris.
In Silico Screening to Identify Inhibitors of Growth Factor Receptor 2–Focal Adhesion Kinase Interaction for Therapeutic Treatment of Pathological Cardiac Hypertrophy
The focal adhesion kinase–growth factor receptor 2 (FAK–Grb2) protein–protein interaction is implicated in pathogenesis of stress-induced cardiac hypertrophy.
A Simulation and Estimation Platform for Malaria Model Evaluation
Accelerating clinical development of new compounds demands efficient systems for evaluation and interpretation of trial results. Systematizing trial evaluation methods yields efficiency and confidence in results.
Developing PBPK for Ocular Delivery
Cooperation grant with the FDA (2014‐2019) a 4‐year funded collaborative project with the FDA Office of Generic Drugs on the development of mechanistic models for ocular delivery
Proprietary modeling platforms to support regulatory interactions: A vendor’s perspective
Proprietary modeling platforms are driving the vast majority of internal R&D activities at companies.
Assessing Effects of Sublingual BHV-0223 and Oral Riluzole on Liver Function Test Parameters
DILIsym is a mechanistic, mathematical model that has been constructed to support pharmaceutical risk assessment and decision making
Applying in silico-in vitro-in vivo Extrapolation (IS-IV-IVE) Techniques to Predict Exposure and Guide Risk Assessment
Applying IS-IV-IVE Techniques to Predict Exposure and Guide Risk Assessment
Pharmacokinetics, Pharmacodynamics, and PKPD Modeling of Curcumin in Regulating Antioxidant and Epigenetic Gene Expression in Healthy Human Volunteers
Curcumin is a major component of the spice turmeric (Curcuma longa), often used in food or as a dietary supplement. Many preclinical studies on curcumin suggest health benefits in many diseases due to its antioxidant/anti-inflammatory and epigenetic effects.
Development of a Quantitative Systems Toxicology Model of Drug-Induced Cholangiocyte Injury in DILIsym
Cholangiocyte injury accounts for a quarter of drug-induced liver injury (DILI) cases and is associated with higher rates of morbidity and mortality than hepatocellular DILI (Chalasani et al., 2015).
Mechanistic analysis and experimental verification of bicarbonate-controlled enteric coat dissolution: Potential in vivo implications
Enteric coatings have shown in vivo dissolution rates that are poorly predicted by traditional in vitro tests, with the in vivo dissolution being considerably slower than in vitro.
Game Changing: The Latest Developments in the Machine Learning/ PBPK/QST Modeling Space
Simulations Plus continues to lead in the areas of PBPK modeling to support regulatory submissions and alternatives to animal testing.
Building a Quantitative Structure-Property Relationship (QSPR) Model
Knowing the physicochemical and general biochemical properties of a compound is critical to understanding how it behaves in different biological environments and to anticipating what is likely to happen in situations where that behavior cannot be measured directly.