The main objective of this study was to develop an in vivo predictive dissolution (IVPD) model for topiroxostat immediate-release (IR) formulation...
April 2021 GastroPlus Newsletter
Happy Spring. For most of the world, we are beginning to come out of our Covid enforced isolation.
Simulations Plus Reports Record Second Quarter Fiscal 2021 Financial Results
Second quarter revenue of $13.1 million, reflecting 27% year-over-year growth
Board of Directors announces quarterly dividend of $0.06 per share
Decomposition Profile Data Analysis for Deep Understanding of Multiple Effects of Natural Products
It is difficult to understand the entire effect of a natural product because such products generally have multiple effects.
Concentration-QTc Analysis of Quizartinib in Patients with Relapsed/Refractory Acute Myeloid Leukemia
This analysis evaluated the relationship between concentrations of quizartinib and its active metabolite AC886 and QT interval corrected using Fridericia's formula (QTcF) in patients with...
Simulations Plus Reports Successful Results from AIDD Collaboration with Large Pharmaceutical Company
80% of preliminary molecules tested exhibit submicromolar activity and acceptable ADME properties
Quantitative systems toxicology (QST) to investigate mechanisms contributing to clinical bilirubin elevations
To be presented at the FDA/CDER and AASLD 2021 DILI Conference XVIII. Quantitative systems toxicology (QST) to investigate mechanisms contributing to clinical bilirubin elevations: Some patients treated with Drug X experienced clinically relevant elevations in serum bilirubin with concomitant ALT elevations, indicative of potentially severe liver injury (Hy’s Law cases). However, the interpretation is complicated if there is evidence that a compound directly alters bilirubin disposition, leading to bilirubin elevations absent liver injury. Distinguishing between these two possibilities is critical to inform drug development decisions. DILIsym, a QST platform of drug-induced liver injury (DILI), was used to investigate the interpretation of putative Drug X-related elevations in liver biomarkers.
Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and (CBD) using Quantitative Systems Toxicology (QST)
To be presented at the FDA/CDER and AASLD 2021 DILI Conference XVIII. Assessing the Potential for Hepatotoxicity for Combination Therapy of Valproate (VPA) and (CBD) using Quantitative Systems Toxicology (QST). We aimed to identify the mechanism(s) accounting for the higher incidence of ALT elevation observed in individuals treated with VPA and CBD by using a Quantitative Systems Toxicology (QST) model of hepatotoxicity (DILIsym®) to test the hypothesis that increased incidence of ALT elevation was due to VPA and CBD (or metabolites of each) inhibiting mitochondrial respiration.
Clinical pharmacokinetic study of latrepirdine via in silico sublingual administration
In recent decades, numerous in silico methodologies have been developed focused on the study of pharmacodynamic, pharmacokinetics and toxicological properties of drugs.
Molecular modeling for potential cathepsin L inhibitor identification as new anti-photoaging agents from tropical medicinal plants
Ultraviolet exposure can cause photoaging toward the human skin which is begun by the inflammation on the exposure area, also resulting in activation of a degradative enzyme cathepsin L.
Basic of machine learning and deep learning in imaging for medical physicists
The manuscript aims at providing an overview of the published algorithms/automation tool for artificial intelligence applied to imaging for Healthcare.
PK/PD modeling of a clazosentan thorough QT study with hysteresis in concentration-QT and RR-QT
Clazosentan's potential QT liability was investigated in a thorough QT study in which clazosentan was administered intravenously as a continuous infusion of 20 mg/h immediately followed by 60 mg/h.
April 2021 News/Events
As they say, April showers bring May flowers...
Prediction of fraction unbound in plasma in children in data-limited scenarios for human health risk assessment
In human health risk assessment, pediatric physiologically-based pharmacokinetic modeling has been used to predict chemical-specific toxicokinetic adjustment factors.
A Phase 1b Study of Oral Chk1 Inhibitor LY2880070 as Monotherapy in Patients with Advanced or Metastatic Cancer
In the context of DNA damage, Checkpoint Kinase 1 (Chk1) mediates a checkpoint response which arrests the cell cycle and allows the cell to complete DNA repair and replication.
Simulations Plus Sets Date for Second Quarter Fiscal Year 2021 Earnings Release and Conference Call
Conference call to be on Monday, April 12, 2021, at 4:15 p.m. ET
The emerging plasticity of SARS-CoV-2
Viruses evolve as a result of mutation (misincorporations, insertions or deletions, and recombination) and natural selection for favorable traits such as more efficient viral replication, transmission, and evasion of host defenses.
Characterization of stress degradation products of nintedanib by UPLC, UHPLC-Q-TOF/MS/MS and NMR: Evidence of a degradation product with a structure alert for mutagenicity
Nintedanib is an anti-cancer drug used for the treatment of idiopathic pulmonary fibrosis and non-small cell lung cancer.
The Future of Clinically Relevant Dissolution Testing and Physiologically Based Biopharmaceutics Modeling (PBBM/PBPK) in Drug Product Development, Manufacturing Changes and Controls
Regulatory applications of dissolution testing as per published FDA guidance...