FDA is open to proposals of using modeling approaches for bioequivalence (BE), or for new drugs,with the proper justification and model verification
Advancing current PBPK model applications to support internal development and regulatory decisions
Numbers of applications (NDA, ANDA) supported by PBPK modeling has increased significantly since 2008.
Physiologically Based Pharmacokinetic Modeling to Evaluate Formulation Factors Influencing Bioequivalence of Metoprolol Extended‐Release Products
The University of Florida Center for Pharmacometrics and Systems Pharmacology and the Food and Drug Administration Office of Generic Drugs have collaborated on a research project to develop...
Evaluating the Clinical Impact of Formulation Variability: A Metoprolol Extended‐Release Case Study
The objective of this research was to evaluate the impact of changes in the formulation of metoprolol extended‐release (ER) tablets on dissolution, pharmacokinetic, and exercise‐induced heart rate (EIHR) using...
Simulations Plus to Present at B. Riley FBR Investor Conference on May 22, 2019
Shawn O’Connor, chief executive officer, will present at the 20th Annual B. Riley FBR Institutional Investor Conference on Wednesday, May 22, at 10:30 a.m. (PDT) in Room 8.
Oxysterols and apolipoproteins in multiple sclerosis: a 5-year follow-up study
The purpose of this work was to investigate whether changes in oxysterol and apolipoprotein levels over 5 years are associated with...
Discovery of Membrane Permeability, Pharmacokinetics Properties and Mechanism of Action for Analogs of Ethylenediamine-N,N′-di-2-(3-Cyclohexyl)Propionic Acid and 1,3-Propandiamine-N,N′-di-2-(3-Cyclohexyl)Propionic Acid with Antiproliferative Activity Using In Vitro and In Silico Methods
In previously in vitro studies on different cell lines and in vivo on melanoma and 4T1 murine breast cancer and metastasis it was shown antiproliferative activity for ester derivatives of (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid, and (S,S)-1,3-propanediamine-N,N′-di-2-(3-cyclohexyl)propanoic acid.
Androgen Receptor and PI3K Pathway Activity in Ovarian Cancer
We sought to evaluate androgen receptor (AR) and PI3K pathway activity in ovarian cancer cell lines and tissue and determine if either pathway was correlated with growth...
Development of a Direct CD8+ T Cell Activation QSP Model for Ovalbumin in the Context of 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.
In Silico and in Vitro Simulations to Predict Idiosyncratic DILI: What is on the Horizon?
Multiple species: human, rat, mouse, and dog, Population variability, The three primary acinar zones of liver represented, Essential cellular processes represented to multiple scales in interacting submodels...
Assessing and Managing DILI Risk in Trials: A Consultant’s Perspective
DILI typically has drug-specific “signatures”: Hepatocellular, cholestatic, mixed (R-value), Latency “window,” Rate of progression, rate of resolution, Extra-hepatic manifestations (e.g. hypersensitivity signs)
Assessing Effects of BHV-0223 40 mg Zydis® Sublingual Formulation and Riluzole 50 mg Oral Tablet on Liver Function Test Parameters Utilizing DILIsym®
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the death of motor neurons that leads to progressive muscle weakness and difficulties in speaking, swallowing, and breathing.
In Silico Prediction of Plasma Concentrations of Fluconazole Capsules with Different Dissolution Profiles and Bioequivalence Study Using Population Simulation
A biowaiver is accepted by the Brazilian Health Surveillance Agency (ANVISA) for immediate-release solid oral products containing Biopharmaceutics Classification System (BCS) class I drugs showing rapid drug dissolution.
Minor structural modifications of bisphenol A strongly affect physiological responses of HepG2 cells
Bisphenols represent a large group of structurally similar compounds.
The Discriminatory Power of the BCS-based Biowaiver: A Retrospective with Focus on Essential Medicines
This article summarizes historic developments, recent expert opinions and (currently) unresolved challenges concerning the Biopharmaceutics Classification System (BCS) based biowaiver.
Analysis of pharmacological mechanisms and targets mining of Wuzi-Yanzong-Wan for treating non-obstructive oligoasthenospermia
As a classical traditional Chinese medicine, Wuzi-Yanzong-Wan (WZYZW) has been widely applied for several centuries to treat non-obstructive oligoasthenozoospermia (NOA), although its pharmacological mechanisms remain largely unknown.
Quantitative Analysis of Tozadenant Using Liquid Chromatography-Mass Spectrometric Method in Rat Plasma and Its Human Pharmacokinetics Prediction Using Physiologically Based Pharmacokinetic Modeling
Tozadenant is one of the selective adenosine A2a receptor antagonists with a potential to be a new Parkinson’s disease (PD) therapeutic drug. In this study, a liquid chromatography-massspectrometry ...
Cu-mediated synthesis of differentially substituted diazepines as AChE inhibitors; validation through molecular docking and Lipinski’s filter to develop novel anti-neurodegenerative drugs
A highly efficient Cu-mediated route for the synthesis of fused [1,2,3]triazolo[1,4]diazepines has been developed by azidation-cyclization of 2-bromo-N-propargylamines in a one-pot fashion.
Enabling Personalized Medicine Through Pharmacokientic Modeling
Personalized medicine strives to deliver the ‘right drug’ at the ‘right dose’ at the ‘right time’ by considering the unique characteristics that define specialized populations of patients and contribute to inter-individual variability...
GastroPlus® User Group Webinar: Applications/Experiences of PBPK Modeling to Support Regulatory Interactions
Recent experiences with PBPK model-based regulatory submissions used to obtain product development and DDI waivers will be discussed.