Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, A Potential Oral Drug Candidate for COVID-19 Treatment

Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, A Potential Oral Drug Candidate for COVID-19 Treatment

Authors: Wang AQ, Hagen NR, Padilha EC, Yang M, Shah P, Chen CZ, Huang W, Terse P, Sanderson P, Zheng W, Xu X
Publication: bioRxiv
Keywords: dose slection, fih, FIHSimulator, first-in-human, gastroplus, IVIVE, mechanistic absorption, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

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: development of a physiologically based pharmacokinetic tool to support human health risks assessments

Authors: Emond C, Multigner L
Publication: Arch Toxicol
Keywords: gastroplus, partition coefficients, PBPK modeling, safety assessment, toxicology
Software: GastroPlus®

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.

Capturing Interpatient Variability with SimPops

Capturing Interpatient Variability with SimPops

Authors: Siler SQ
Conference: ASCPT
Keywords: AEC, CARDIOsym, clinical, clinical data, DILIsym, disease progression, DLCO, fibrosis, FVC, Genetic algorithms, honeycombing, HRCT, ILDsym, immune, IPFsym, KIDNEYsym, lung collagen, mediator, MITOsym, model, NAFLDsym, pathophysiology, pirfenidone, proteoglycan, quantitative systems pharmacology (QSP), Quantitative Systems Toxicology (QST), RENAsym, SimPops, treatment
Software: CARDIOsym, DILIsym®, ILDsym™, IPFsym®, KIDNEYsym, MITOsym®, NAFLDsym®, RENAsym®
Division: Quantitative Systems Pharmacology (QSP)

SimPops provide significant value for drug development. "The SimPops are the Crown Jewel".

Synthesis and Characterization of Novel 2-Pyridine Mono(thio)carbohydrazones as Promising Antioxidant and Antimicrobial Agents. Experimental and Theoretical Approach

Synthesis and Characterization of Novel 2-Pyridine Mono(thio)carbohydrazones as Promising Antioxidant and Antimicrobial Agents. Experimental and Theoretical Approach

Authors: Mrdan G, Tot A, Vranes M, Raseta M, Knežević P, Verbic T, Matijević BM
Publication: Experimental and Theoretical Approach
Keywords: biological activity, hydrazones, TD-DFT
Software: ADMET Predictor®
Therapeutic Areas: Anti-effective

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

Applications of PBPK/PBBM modeling in generic product development: An industry perspective

Authors: Yuvaneshwari K, Kollipara S, Ahmed T, Chachad S
Publication: J Drug Deliv Sci Technol
Keywords: dissolution safe space, food effect, gastroplus, mechanistic absorption model, pbbm, PBPK modeling, physiologically based biopharmaceutics, vbe, virtual bioequivalence
Software: GastroPlus®

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

Assessment of the predictive capability of modelling and simulation to determine bioequivalence of inhaled drugs: A systematic review

Authors: Rebello J, Brashier B, Shukla S
Publication: Daru Jour Pharma Sci
Keywords: gastroplus, inhaled dosing, PBPK modeling, pcat, physiologically based pharmacokinetics, population simulations, pulmonary modeling, pulmonary playlist, virtual bioequivalence
Software: GastroPlus®

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

Alternative experimental approaches to reduce animal use in biomedical studies

Authors: Lee SY, Lee DY, Kang JH, Jeong JW, Kim JH, Kim HW, Oh DH, Kim JM, Rhim SJ, Kim GD, Kim HS, Jang YD, Park Y, Hura SJ
Publication: J Drug Deliv Sci Technol
Keywords: Alternative animal study, Biomedicine, in vitro models, Invertebrate model, Organ-on-a-chip
Software: ADMET Predictor®

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

Dose Number as a Tool to Guide Lead Optimization for Orally Bioavailable Compounds in Drug Discovery

Authors: Wuelfing WP, El Marrouni A, Lipert MP, Daublain P, Converso A, Templeton AC
Publication: J Med Chem
Keywords: formulation assessment, gastroplus, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: GastroPlus®

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

Predictive Performance of Next Generation Human Physiologically Based Kinetic (PBK) Models Based on In Vitro and In Silico Input Data

Authors: Punt A, Louisse J, Beekmann K, Pinckaers N, Fabian E, van Ravenzwaay B, Carmichael PL, Sorrell I, Moxon TE
Publication: Altex
Keywords: Cmax, human, in silico, in vitro, pbk, PBPK, QIVIVE
Software: ADMET Predictor®

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

In silico predictions of absorption of MDI substances after dermal or inhalation exposures to support a category based read-across assessment

Authors: Bartels M, van Osdol W, Le Merdy M, Chappelle A, Kuhl A, West R
Publication: Regul Toxicol Pharmacol
Keywords: admet predictor, gastroplus, inhaled, PBPK modeling, pulmonary, pulmonary playlist, risk assessment, safety assessment, Toxicity, toxicokinetics
Software: GastroPlus®
Division: PBPK

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

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

Authors: Hussain A, Afzal O, Altamimi ASA, Ali A, Martinez F, Siddique MUM, Acree WE
Publication: Journal Molecular Liquids
Keywords: biopharmaceutics, dissolution kinetics, formulation assessment, gastroplus, mechanistic absorption, pbbm, PBPK modeling
Software: GastroPlus®

(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.