Quantitative Systems Toxicology (QST) Modeling Using a New Virtual Population in BIOLOGXsym Offers Mechanistic Insights Into Bile Acid-mediated Biologics-induced Liver Injury (BILI) Upon Cimaglermin Alfa (GGF2) Administration

Quantitative Systems Toxicology (QST) Modeling Using a New Virtual Population in BIOLOGXsym Offers Mechanistic Insights Into Bile Acid-mediated Biologics-induced Liver Injury (BILI) Upon Cimaglermin Alfa (GGF2) Administration

Authors: Beaudoin J, Vernetti L, Taylor DL, Gough A, Clemens L, Battista C, Siler SQ, Shoda LKM, Howell BA, Yang K
Conference: American College of Toxicology (ACT)
Keywords: ACT 2023, alanine aminotransferase (ALT), BILI, BIOLOGXsym, GGF2, hepatotoxicity, Quantitative Systems Toxicology (QST)
Software: BIOLOGXsym
Division: DILIsym Services

Biopharmaceuticals are increasingly used to treat various medical conditions, but BILI events can end...

Advancing the Multi-Targeted Mechanisms of Action of a Mitochondrial Activator (AXA1125) for Treating NASH Using a Quantitative Systems Pharmacology Model

Advancing the Multi-Targeted Mechanisms of Action of a Mitochondrial Activator (AXA1125) for Treating NASH Using a Quantitative Systems Pharmacology Model

Authors: Lakhani VV, Gao M, Hinderliter P, Russel M, Azer K, Siler SQ
Conference: AASLD
Keywords: AASLD liver meeting, NAFLD, NAFLDsym, NASH, QSP model, quantitative systems pharmacology (QSP), treatment
Software: NAFLDsym®
Division: DILIsym Services

Patients with non-alcoholic steatohepatitis (NASH) do not currently have options for pharmaceutical...

SHIP1 therapeutic target enablement: Identification and evaluation of inhibitors for the treatment of late-onset Alzheimer’s disease

SHIP1 therapeutic target enablement: Identification and evaluation of inhibitors for the treatment of late-onset Alzheimer’s disease

Authors: Jesudason CD, Mason ER, Chu S, Oblak AL, Javens-Wolfe J, Moussaif M, Durst G, Hipskind PA, Beck DE, Dong J, Amarasinghe O, Zhang ZY, Hamdani AK, Singhal K, Mesecar AD, Souza S, Jacobson MP, Salvo JD, Soni DM, Kandasamy M, Masters AR, Quinney SK, Doolen S, Huhe H, Rizzo SJS, Lamb BT, Palkowitz AD, Richardson TI
Publication: Alzheimers Dement
Keywords: admet predictor, fih, first-in-human, gastroplus, in vitro–in vivo extrapolation, IVIVE, PBPK modeling, physiologically based pharmacokinetics
Software: ADMET Predictor®, GastroPlus®

The risk of developing Alzheimer's disease is associated with genes involved in microglial function.

Predicting the pharmacokinetics and pharmacodynamics of antisense oligonucleotides: an overview of various approaches and opportunities for PBPK/PD modelling

Predicting the pharmacokinetics and pharmacodynamics of antisense oligonucleotides: an overview of various approaches and opportunities for PBPK/PD modelling

Authors: Gao X, Diep JK, Norris DA, Yu RZ, Geary RS
Publication: Expert Opin Drug Metab Toxicol
Keywords: dose selection, gastroplus, PBPK modeling, pbpk/pd, pharmacodynamics, physiologically based pharmacokinetics, PK/PD, tissue concentrations
Software: GastroPlus®

Advances in research and development (R&D) have enabled many approvals of antisense oligonucleotides (ASOs). Its administration expanded from systemic to local for treating various diseases, where predicting target tissue exposures and pharmacokinetics (PK) and pharmacodynamics (PD) in human can be critical.

Physiologically Based Pharmacokinetic modelling of drugs in pregnancy: A mini-review on availability and limitations

Physiologically Based Pharmacokinetic modelling of drugs in pregnancy: A mini-review on availability and limitations

Authors: Berezowska M, Sharma P, Pilla Reddy V, Coppola P
Publication: Fundam Clin Pharmacol
Keywords: fetus, gastroplus, neonates, PBPK modeling, physiologically based pharmacokinetics, pregnant women, special populations
Software: GastroPlus®

Physiologically based pharmacokinetic (PBPK) modelling in pregnancy is a relatively new approach that is increasingly being used to assess drug systemic exposure in pregnant women to potentially inform dosing adjustments.

ILDSYM®, A Quantitative Systems Pharmacology (QSP) Platform, Successfully Simulates Efficacy of Key Treatments for Systemic Sclerosis-Interstitial Lung Disease

ILDSYM®, A Quantitative Systems Pharmacology (QSP) Platform, Successfully Simulates Efficacy of Key Treatments for Systemic Sclerosis-Interstitial Lung Disease

Authors: Kenz Z, Yang K, Battista C, Shoda LKM, Siler SQ
Conference: ACoP
Keywords: ACoP2023, ILDsym, interstitial lung disease (ILD), lung diseases, nintedanib, quantitative systems pharmacology (QSP), systemic sclerosis, Systemic Sclerosis-Interstitial Lung Disease (SSc-ILD), Tocilizumab
Software: ILDsym™
Division: DILIsym Services

Systemic sclerosis (SSc) is a rare connective tissue and autoimmune disease associated with inflammation of the skin and internal organs. Interstitial lung disease (ILD), a frequent complication of SSc with highly variable course, is associated with increased morbidity and mortality risk¹. Two FDA-approved treatments, anti-inflammatory tocilizumab (TCZ) and anti-fibrotic nintedanib (NIN)...

Accelerating a QSP Model of Nonalcoholic Steatohepatitis (NASH) Using the Julia Language

Accelerating a QSP Model of Nonalcoholic Steatohepatitis (NASH) Using the Julia Language

Authors: McDaniel MC, Generaux GT, Huizar F, Berry C, Siler SQ
Conference: ACoP
Keywords: ACoP2023, Julia, Matlab, NAFLD, NAFLDsym, NASH, quantitative systems pharmacology (QSP)
Software: NAFLDsym®
Division: DILIsym Services

NAFLDsym® is a quantitative systems pharmacology (QSP) platform that simulates progression and treatment of nonalcoholic fatty liver...

Contribution of the Dynamic Intestinal Absorption Model (Diamod) to the Development of a Patient-Centric Drug Formulation

Contribution of the Dynamic Intestinal Absorption Model (Diamod) to the Development of a Patient-Centric Drug Formulation

Authors: Moens F, Larsson A, De Blaiser A, Vandevijver G, Spreafico F, Nicolas JM, Lacombe L, Segregur D, Flanagan T, Berben P
Publication: Mol Pharm
Keywords: biopharmaceutics, formulation assessment, gastroplus, in vitro dissolution, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: GastroPlus®

Compound X is a weak basic drug targeting the early stages of Parkinson’s disease, for which a theoretical risk assessment has indicated that elevated gastric pH conditions could potentially result in reduced plasma concentrations.

Mechanistic Representation of NAG Release in Relation to Renal Proximal Tubular Cellular Injury

Mechanistic Representation of NAG Release in Relation to Renal Proximal Tubular Cellular Injury

Authors: Hamzavi N, Bhargava P, Stahl SH, Howell BA, Woodhead JL
Conference: American Society of Nephrology (ASN) Kidney Week
Keywords: Acute kidney injury (AKI), cisplatin, CsA, Kidney Week, N-acetyl-beta-D-glucosaminidase, NAG, Quantitative Systems Toxicology (QST), renal injury, RENAsym
Software: RENAsym®
Division: DILIsym Services

Novel Acute kidney injury (AKI) biomarkers enhance disease understanding and aid...

Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms

Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms

Authors: De Sutter PJ, Gasthuys E, Vermeulen A
Publication: J Pharmacokinet Pharmacodyn
Keywords: biologics, gastroplus, Injectables, injections, large molecules, PBPK modeling, physiologically based pharmacokinetics, tissue concentrations, translational pk
Software: GastroPlus®

Physiologically based pharmacokinetic (PBPK) models can be used to leverage physiological and in vitro data to predict monoclonal antibody (mAb) concentrations in serum and tissues.

Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms

Comparison of monoclonal antibody disposition predictions using different physiologically based pharmacokinetic modelling platforms

Authors: De Sutter PJ, Gasthuys E, Vermeulen A
Publication: J Pharmacokinet Pharmacodyn
Keywords: antibodies, biologics, gastroplus, mab, PBPK modeling, physiologically based pharmacokinetics, tissue concentrations
Software: GastroPlus®

Physiologically based pharmacokinetic (PBPK) models can be used to leverage physiological and in vitro data to predict monoclonal antibody (mAb) concentrations in serum and tissues.

Use of In silico Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach

Use of In silico Methodologies to Predict the Bioavailability of Oral Suspensions: A Regulatory Approach

Authors: Honório TDS, Simon A, Machado RMC, Rodrigues CR, do Carmo FA, Cabral LM, de Sousa VP
Publication: Curr Pharm Des
Keywords: ACAT, dissolution specifications, gastroplus, IVIVC, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: GastroPlus®

Oral suspensions are heterogeneous disperse systems, and the particle size distribution, crystalline form of the dispersed solid, and composition of the formulation can be listed as parameters that control the drug dissolution rate and its bioavailability.

Voices in Molecular Pharmaceutics: Meet Dr. Bart Hens, A Sociable Scientist Focusing on Multidisciplinary Connections to Unravel the Gaps of Oral Drug Behavior in the Human Gastrointestinal Tract

Voices in Molecular Pharmaceutics: Meet Dr. Bart Hens, A Sociable Scientist Focusing on Multidisciplinary Connections to Unravel the Gaps of Oral Drug Behavior in the Human Gastrointestinal Tract

Authors: Hens B
Publication: Mol Pharm
Keywords: biopharmaceutics, gastroplus, pbbm, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Bart Hens (Pharm.D., Ph.D.) holds a Ph.D. degree in Pharmaceutical Sciences obtained from KU Leuven (Supervisor: Prof. Dr. Patrick Augustijns - Leuven, Belgium).