Preclinical pharmacokinetics (PK) and in vitro ADME properties of GS-441524, a potential oral agent for the treatment of Covid-19, were studied. GS-441524 was stable in vitro in liver microsomes, cytosols, and hepatocytes of mice, rats, monkeys, dogs, and humans.
Chlordecone: development of a physiologically based pharmacokinetic tool to support human health risks assessments
Chlordecone (CD; Kepone™) is a carcinogenic organochlorine insecticide with neurological, reproductive, and developmental toxicity that was widely used in the French West Indies (FWI) from 1973 to 1993 to fight banana weevils.
Synthesis and Characterization of Novel 2-Pyridine Mono(thio)carbohydrazones as Promising Antioxidant and Antimicrobial Agents. Experimental and Theoretical Approach
Four new derivatives of 2-pyridine mono(thio)carbohydrazones were synthesized by condensation of carbaldehydes with carbohydrazide and thiocarbohydrazide following a known procedure.
Applications of PBPK/PBBM modeling in generic product development: An industry perspective
Physiologically based pharmacokinetic (PBPK) modeling and physiologically based biopharmaceutics modeling (PBBM) are invaluable tools with wide applications during drug discovery and development stages.
Assessment of the predictive capability of modelling and simulation to determine bioequivalence of inhaled drugs: A systematic review
There are a multitude of different modelling techniques that have been used for inhaled drugs.
Alternative experimental approaches to reduce animal use in biomedical studies
We review experimental approaches that can be used instead of in vivo studies involving vertebrate animal models and human clinical trials.
Dose Number as a Tool to Guide Lead Optimization for Orally Bioavailable Compounds in Drug Discovery
Small molecule developability challenges have been well documented over the last two decades.
Predictive Performance of Next Generation Human Physiologically Based Kinetic (PBK) Models Based on In Vitro and In Silico Input Data
The goal of the present study was to assess the predictive performance of a generic human physiologically based kinetic (PBK) model based on in vitro and in silico input data and the effect of using different input approaches for chemical parameterization on those predictions.
In silico predictions of absorption of MDI substances after dermal or inhalation exposures to support a category based read-across assessment
Methylenediphenyl diisocyanate (MDI) substances used polyurethane production can range from their simplest monomeric forms (e.g., 4,4′-MDI) to mixtures of the monomers with various homologues, homopolymer, and prepolymer derivatives.
Preferential solvation study of (Z)-N-benzyl-2-{5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (3) in {NMP (1) + Water (2)} co-solvent mixture and GastroPlus software based in vitro simulation
(Z)-N-benzyl-2-{5-(4-hydroxybenzylidene)-2,4-dioxothiazolidin-3-yl)acetamide (3) (SE11) is a newly synthesized benzylidine thiazolidinedione to inhibit aldose reductase (AR) to control Diabetes Mellitus (DM) and related complications.
Dissolution Challenges Associated with the Surface pH of Drug Particles: Integration into Mechanistic Oral Absorption Modeling
The present work aimed to differentiate between in vitro dissolution profiles of ibuprofen as input for GastroPlus™ and to see the impact on systemic exposure.
Population Pharmacokinetic Modeling and Exposure-Response Analysis for Aripiprazole Once Monthly in Subjects With Schizophrenia
An intramuscular formulation of aripiprazole monohydrate dosed once monthly (AOM) was developed to address nonadherence with
Preferential Solvation Study of the Synthesized Aldose Reductase Inhibitor (SE415) in the {PEG 400 (1) + Water (2)} Cosolvent Mixture and GastroPlus-Based Prediction
(Z)-N-Benzyl-2-{2,4-dioxo-5-(4-prop-2-yl-1-yloxyl)benzylidene)thiazolin-3-yl)}acetamide (SE415) is a novel aldose reductase inhibitor used in the management of diabetes mellitus (DM) and associated complications.
In Vitro and In Silico Study of Analogs of Plant Product Plastoquinone to Be Effective in Colorectal Cancer Treatment
Plants have paved the way for the attainment of molecules with a wide-range of biological activities.
Transition from Syringe to Autoinjector Based on Bridging Pharmacokinetics and Pharmacodynamics of the P2Y12 Receptor Antagonist Selatogrel in Healthy Subjects
Selatogrel is a potent, reversible, and selective antagonist of the platelet P2Y12 receptor currently developed for the treatment of acute myocardial infarction (AMI).
Level A IVIVC for immediate release tablets confirms in vivo predictive dissolution testing for ibuprofen
A bioequivalence study comparing two fixed dose combination tablets containing 200 mg ibuprofen and 30 mg pseudoephedrine hydrochloride showed bioequivalence for pseudoephedrine AUC and Cmax, but the reference product showed higher Cmax than the test product in fasted conditions.
Identification of phenylcarbamoylazinane-1,3,4-oxadiazole amides as lipoxygenase inhibitors with expression analysis and in silico studies
In search for new anti-inflammatory agents that inhibit the enzymes of arachidonic acid pathway as the drug targets, the present article describes the screening...
A novel chemical inhibitor suppresses breast cancer cell growth and metastasis through inhibiting HPIP oncoprotein
Increasing evidence suggests the pivotal role of hematopoietic pre-B-cell leukemia transcription factor (PBX)-interacting protein (HPIP/PBXIP1) in cancer development and progression...
Best practices in current models mimicking drug permeability in the gastrointestinal tract – an UNGAP review
The absorption of orally administered drug products is a complex, dynamic process, dependant on a range of biopharmaceutical properties; notably the aqueous solubility of a molecule, stability within the gastrointestinal tract (GIT) and permeability.
In Vitro and In Vivo Bioequivalence Study of 3D-Printed Instant-Dissolving Levetiracetam Tablets and Subsequent Personalized Dosing for Chinese Children Based on Physiological Pharmacokinetic Modeling
Recently, the development of Binder Jet 3D printing technology has promoted the research and application of personalized formulations, which are especially useful for children’s medications.