This study was initiated for investigating the possible gastro-transformations that may affect the integrity and safety of the most commonly administered analgesic and antipyretic, paracetamol (PCM).
Bridging in vitro dissolution and in vivo exposure for acalabrutinib. Part I. Mechanistic modelling of drug product dissolution to derive a P-PSD for PBPK model input
Drug product dissolution for four batches of acalabrutinib 100 mg capsules were analyzed with in vitro dissolution in various pH conditions and in media containing synthetic surfactant micelles or biorelevant micelles.
Bridging in vitro dissolution and in vivo exposure for acalabrutinib. Part II. A mechanistic PBPK model for IR formulation comparison, proton pump inhibitor drug interactions, and administration with acidic juices
Acalabrutinib (Calquence®) 100 mg (bid) has received accelerated approval by FDA for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
Concepts of Artificial Intelligence for Computer-Assisted Drug Discovery
Artificial intelligence (AI), and, in particular, deep learning as a subcategory of AI, provides opportunities for the discovery and development of innovative drugs.
1-Methyl-1,2,3,4-tetrahydroisoquinoline – The toxicological research on an exo/endogenous amine with antidepressant-like activity – In vivo, in vitro and in silico studies
1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) demonstrates significant neuroprotective activity.
A repository of protein abundance data of drug metabolizing enzymes and transporters for applications in physiologically based pharmacokinetic (PBPK) modelling and simulation
Population factors such as age, gender, ethnicity, genotype and disease state can cause inter-individual variability in pharmacokinetic (PK) profile of drugs.
Integration of In Silico Pharmacokinetic Modeling Approaches Into In Vitro Dissolution Profiles to Predict Bioavailability of a Poorly Soluble Compound
The objective of present study is to develop pharmacokinetic (PK) prediction methods using in silico PK model for oral immediate release drug products (i.e. solution, suspension, and amorphous solid dispersion).
Reactivation potency of two novel oximes (K456 and K733) against paraoxon-inhibited acetyl and butyrylcholinesterase: In silico and in vitro models
Organophosphates (OPs) irreversibly inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes.
Verubecestat Pharmacokinetic and Exposure-Response Results From APECS, a Phase 3 Trial in Prodromal Alzheimer’s Disease
The BACE inhibitor verubecestat (MK-8931) demonstrated cognitive and functional decline relative to placebo in a 2-year Phase 3 trial of individuals with prodromal AD (APECS; NCT01953601), along with...
In silico Tools at Early Stage of Pharmaceutical Development: Data Needs and Software Capabilities
In early drug development, the selection of a formulation platform and decisions on formulation strategies have to be made within a short timeframe and often with minimal use of the active pharmaceutical ingredient (API).
Towards a TREK-1/2 (TWIK-Related K+ Channel 1 and 2) dual activator tool compound: Multi-dimensional optimization of BL-1249
This letter describes a focused, multi-dimensional optimization campaign around BL-1249, a fenamate class non-steroidal anti-inflammatory and a known activator of the K2P potassium channels TREK-1 (K2P2.1) and TREK-2 (K2P10.1).
Computational Model To Predict the Fraction of Unbound Drug in the Brain
Knowing the value of the unbound drug fraction in the brain (fu,brain) is essential in estimating its effects and toxicity on the central nervous system (CNS)...
Novel isoxazole derivatives as potential antiparkinson agents: synthesis, evaluation of monoamine oxidase inhibitory activity and docking studies
Selective monoamine oxidase B inhibitors are potential drug candidates for the treatment of Parkinson’s disease.
Computational Systems Pharmacology-Target Mapping for Fentanyl-Laced Cocaine Overdose
The United States of America is fighting against one of its worst-ever drug crises.
In-silico Approaches to Study Therapeutic Efficacy of Nutraceuticals
Medicinal plants are sources of bioactive compounds for curing ailments since ages.
Requirements to Establishing Confidence in Physiologically Based Pharmacokinetic (PBPK) Models and Overcoming Some of the Challenges to Meeting Them
When scientifically well-founded, the mechanistic basis of physiologically based pharmacokinetic (PBPK) models can help reduce the uncertainty and increase confidence in extrapolations outside the studied scenarios or studied populations.
In Silico Prediction of Isoliquiritigenin and Oxyresveratrol Compounds to BCL-2 dan VEGF-2 Receptors
Isoliquiritigenin and oxyresveratrol are compounds that have been reported to have anticancer activities.
Overview of Brazilian Requirements for Therapeutic Equivalence of Orally Inhaled and Nasal Drug Products
Brazil has established a framework for provision of generic pharmaceuticals including for orally inhaled and nasal drug products (OINDP) to its populace.
Stability behaviour of antiretroviral drugs and their combinations. 10: LC-HRMS, LC-MSn, LC-NMR and NMR characterization of fosamprenavir degradation products and in silico determination of their ADMET properties
The present study focused upon the forced degradation behaviour of fosamprenavir (FPV), an antiretroviral drug. A total of six degradation products (DPs) were separated on a non-polar stationary phase by high performance liquid chromatography (HPLC).
Impact of Intracellular Concentrations on Metabolic Drug-Drug Interaction Studies
Accurate prediction of drug-drug interactions (DDI) is a challenging task in drug discovery and development. It requires determination of enzyme inhibition in vitro which is highly system-dependent for many compounds.