This report summarizes the proceedings of Session 1 of the one-day public workshop titled “Advances in PBPK Modeling and its Regulatory Utility for Oral Drug Product Development” hosted by the U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) on October 12, 2023.
PBPK Modeling to Support Bioavailability and Bioequivalence Assessment in Pediatric Populations
This report summarizes the proceedings for Session 3 of the one-day public workshop entitled “Advances in PBPK Modeling and its Regulatory Utility for Oral Drug Product Development” a jointly sponsored workshop by U.S. Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) on October 12, 2023.
In Vitro and In Vivo Pharmacokinetic Characterization of 7-Hydroxymitragynine, an Active Metabolite of Mitragynine, in Sprague-Dawley Rats
Kratom, a Southeast Asian tree, has been researched for its potential as a therapeutic for substance use disorders.
Antiviral Activity of Halogenated Compounds Derived from L-Tyrosine Against SARS-CoV-2
Currently, there are no effective medications for treating all the clinical conditions of patients with COVID-19.
Trends in Drug-Drug Interactions for New Drug Clinical Trials in China Over the Past 10 Years (2013–2022)
The number of drug-drug interaction (DDI) clinical trials in China has increased rapidly in recent years.
Unveiling the Phenolic Profiling of Moroccan Ferula communis L. Fruits: A Combination of In Silico and In Vivo Protective Effect Against Methotrexate-Induced Hepato-Renal Dysfunction
Methotrexate (MTX) is associated with several side effects, including hepatic and renal toxicities, which limit its effectiveness as an anticancer medication.
Molluscicidal and Schistosomicidal Activities of 2-(1H-Pyrazol-1-yl)-1,3,4-thiadiazole Derivatives
Schistosomiasis is caused by flatworms of the genus Schistosoma, for which mollusks of the genus Biomphalaria are intermediate hosts.
Leveraging Omeprazole PBPK/PD Modeling to Inform Drug–Drug Interactions and Specific Recommendations for Pediatric Labeling
Omeprazole is widely used for managing gastrointestinal disorders like GERD, ulcers, and H. pylori infections.
Physiologically Based Pharmacokinetic Models for Infliximab, Ipilimumab, and Nivolumab Developed with GastroPlus to Predict Hepatic Concentrations
Infliximab, ipilimumab, and nivolumab are three monoclonal antibodies that have been associated with hepatotoxicity.
RSM and AI Based Machine Learning for Quality by Design Development of Rivaroxaban Push-Pull Osmotic Tablets and its PBPK Modeling
The study is based on applying Artificial Neural Network (ANN) based machine learning and Response Surface Methodology (RSM) as simultaneous bivariate approaches in developing controlled-release rivaroxaban (RVX) osmotic tablets.
A Physiologically Based Pharmacokinetic Model of an Oral Tyrosine Kinase 2 Inhibitor Deucravacitinib in Healthy Adults
This study presents the first physiologically based pharmacokinetic (PBPK) model for deucravacitinib, a novel oral selective tyrosine kinase 2 (TYK2) inhibitor approved for treating moderate-to-severe plaque psoriasis.
Breaking Barriers in PROTAC Design: Improving Solubility of USP7-Targeting Degraders
The development of von Hippel–Lindau (VHL) hijacking proteolysis-targeting chimeras (PROTACs) has been hindered by suboptimal physicochemical properties, including high total polar surface area (TPSA), high hydrogen bond donor (HBD) counts, and poor solubility.
Modeling Carbon Basicity
This work presents a predictive model of aqueous ionization constants (pKa) of protonatable carbons in certain aromatic rings.
Next Generation Risk Assessment of Hair Dye HC Yellow no. 13: Ensuring Protection from Liver Steatogenic Effects
This study employs animal-free Next Generation Risk Assessment (NGRA) principles to evaluate the safety of repeated dermal exposure to 2.5% (w/w) HC Yellow No. 13 (HCY13) hair dye.
Leveraging Model Master Files from a Technology Company Perspective: Facilitating Quantitative Medicine in Regulatory Frameworks
Model Master Files (MMFs) offer a much needed approach to integrating computational modelling into drug development and regulatory frameworks, supporting the growth of quantitative medicine.
Assessment of Liver Injury Potential of Investigational Medicines in Drug Development
Drug-induced liver injury (DILI) is rare in clinical practice but when it occurs it can lead to acute liver failure and death. Drug developers and regulators undertake a series of steps to identify the DILI potential of a medication before it is approved for marketing.
Hepatotoxicity Evaluation of Levornidazole and Its Three Main Impurities: Based on Structure–Toxicity Classification Prediction Combined with Zebrafish Toxicity Assessment
Levornidazole, a nitroimidazole compound, has been linked to hepatotoxic adverse effects in clinical settings.
Hansen Solubility Parameters, Computational, and Thermodynamic Models for Tofacitinib Citrate Solubility in Neat Mono Solvents, and GastroPlus Based Predicted In Vivo Performance of Subcutaneous Solution in Humans
We investigated the experimental solubility of tofacitinib citrate (TNF) in HSPiP predicted mono solvents at varied temperature points, followed by validation with various models (computational and thermodynamic) and GastroPlus based predicted in-vivo performance in individuals (adult humans).
Physiologically Based Pharmacokinetic Model for Oxcarbazepine Active Metabolite to Predict Pharmacokinetics in Paediatric Patients with Renal Impairment and Adjust Dosages
Oxcarbazepine (OXC) has been approved as monotherapy or adjunctive therapy for paediatric partial seizures.
Roles of Supersaturation and Liquid–Liquid Phase Separation for Enhanced Oral Absorption of Poorly Soluble Drugs from Amorphous Solid Dispersions
Amorphous solid dispersion (ASD) is one of the most important enabling formulation technologies for the development of poorly soluble drugs.