Human health risk assessment is historically built upon animal testing, often following Organisation for Economic Co-operation and Development (OECD) test guidelines and exposure assessments.
Development of an extemporaneous preparation formulation using a simple and non-solubilizing matrix for first in human clinical study
Extemporaneous preparation (EP) formulation is an attractive strategy to accelerate the formulation development of new chemical entities for first entry into human study.
Integrating Artificial Intelligence for Drug Discovery in the Context of Revolutionizing Drug Delivery
Drug development is expensive, time-consuming, and has a high failure rate.
Accurate Prediction of Kp,uu,brain Based on Experimental Measurement of Kp,brain and Computed Physicochemical Properties of Candidate Compounds in CNS Drug Discovery
A mathematical equation model was developed by building the relationship between the fu,b/fu,p ratio and the computed physicochemical properties of candidate compounds, thereby predicting Kp,uu,brain based on a single experimentally measured Kp,brain value.
Chronic kidney disease and physiologically based pharmacokinetic modeling: a critical review of existing models
Physiologically based pharmacokinetic (PBPK) modeling is a paradigm shift in this era for determining the exposure of drugs in pediatrics, geriatrics, and patients with chronic diseases where clinical trials are difficult to conduct.
Application of a new MDCKII-MDR1 cell model to measure the extent of drug distribution in vitro at equilibrium for prediction of in vivo unbound brain-to-plasma drug distribution
Reliable estimates of drug uptake from blood to brain parenchyma are crucial in CNS drug discovery and development.
Using Mechanistic Modeling Approaches to Support Bioequivalence Assessments for Oral Products
This report summarizes the proceedings for Day 1 Session 3 of the 2-day public workshop entitled “Best Practices for Utilizing Modeling Approaches to Support Generic Product Development,” a jointly sponsored workshop by the US Food and Drug Administration (FDA) and the Center for Research on Complex Generics (CRCG) in the year 2022.
Evaluating Utilization of Tiny-TIM to Assess the Effect of Food on the Absorptions of Oral Drugs and Its Application on Biopharmaceutical Modeling
Safety and efficacy are the most critical factors for the development of modern medications.
Population pharmacokinetics of the dual endothelin receptor antagonist aprocitentan in subjects with or without essential or resistant hypertension
Aprocitentan is a novel, potent, dual endothelin receptor antagonist that recently demonstrated efficacy in the treatment of difficult-to-treat (resistant) hypertension.
Using molecularly dissolved drug concentrations in PBBMs improves the prediction of oral absorption from supersaturating formulations
Predicting the absorption of drugs from enabling formulations is still challenging due to the limited capabilities of standard physiologically based biopharmaceutics models (PBBMs) to capture complex absorption processes.
Assessing the utility of in silico tools in early drug development: The case of a pharmaceutically relevant formulation of the prodrug psilocybin
Depressive disorders contribute to an excruciating global mental health burden.
Exploring the impact of CYP2D6 and UGT2B7 gene-drug interactions, and CYP-mediated DDI on oxycodone and oxymorphone pharmacokinetics using physiologically-based pharmacokinetic modeling and simulation
Oxycodone is one of the most commonly used opioids to treat moderate to severe pain.
Preclinical characterization of the absorption and disposition of the brain penetrant PI3K/mTOR inhibitor paxalisib and prediction of its pharmacokinetics and efficacy in human
Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults.
PBPK Modeling Approach to Predict the Behavior of Drugs Cleared by Metabolism in Pregnant Subjects and Fetuses
This study aimed to develop a physiologically based pharmacokinetic (PBPK) model that simulates metabolically cleared compounds’ pharmacokinetics (PK) in pregnant subjects and fetuses.
Pharmacokinetic model of human exposure to ciprofloxacin through consumption of fish
Fluoroquinolones are broad-spectrum antibiotics that accumulate in the environment.
Use of the Same Model or Modeling Strategy Across Multiple Submissions: Focus on Complex Drug Products
Evidence shows that there is an increasing use of modeling and simulation to support product development and approval for complex generic drug products in the USA, which includes the use of mechanistic modeling and model-integrated evidence (MIE).
An Integrated Computational Approaches for Designing of Potential Piperidine based Inhibitors of Alzheimer Disease by Targeting Cholinesterase and Monoamine Oxidases Isoenzymes
The study aimed to evaluate the potential of piperidine-based 2H chromen-2-one derivatives against targeted enzymes, i.e., cholinesterase’s and monoamine oxidase enzymes.
Oligoadenylate Synthetases 1 Enhances DNA Sensor Cgas Translation to Mediate Antiviral Activity
Oligoadenylate synthetases (OAS) are a family of interferon (IFN)-stimulated genes known to inhibit viral replication through the enzymatic synthesis of 2'-5' oligoadenylates and activation of Ribonuclease L.
Prediction of pharmacokinetics of an anaplastic lymphoma kinase inhibitor in rat and monkey: application of physiologically based pharmacokinetic model as an alternative tool to minimise animal studies
The pharmacokinetic (PK) and toxicokinetic profile of a drug from its preclinical evaluation helps the researcher determine whether the drug should be tested in humans based on its safety and toxicity.
Novel application of PBBM to justify impact of faster dissolution on safety and pharmacokinetics – a case study and utility in regulatory justifications
Physiologically based biopharmaceutics modelling (PBBM) was recognised as potential approach for biopharmaceutics applications.