Investigating the Potential Hepatotoxicity of ORM-48824 in a Quantitative Systems Toxicology Platform for Liver Safety, DILIsym®

Investigating the Potential Hepatotoxicity of ORM-48824 in a Quantitative Systems Toxicology Platform for Liver Safety, DILIsym®

Authors: Bhargava P, Tallapaka SB, Korjamo T, Howell BA, Malinen M, Oinonen T
Conference: SOT
Keywords: DILIsym, hepatoxicity, liver safety, MITOsym, QST, Quantitative Systems Toxicology (QST)
Software: DILIsym®, MITOsym®
Division: Quantitative Systems Pharmacology (QSP)

ORM-48824 is a transient receptor potential Ankyrin-1 (TRPA1) antagonist and was initially being developed for patients with diabetic neuropathic pain...

Prediction of Multidrug Resistance Protein 3 (MDR3) Inhibition-mediated Cholestatic Drug-induced Liver Injury (DILI) Using Quantitative Systems Toxicology (QST) Modeling

Prediction of Multidrug Resistance Protein 3 (MDR3) Inhibition-mediated Cholestatic Drug-induced Liver Injury (DILI) Using Quantitative Systems Toxicology (QST) Modeling

Authors: Beaudoin J, Adiwidjaja J, Yang K, Woodhead JL
Conference: SOT
Keywords: DILIsym, drug induced liver injury (DILI), modeling, multidrug resistance protein 3 (MDR3), Quantitative Systems Toxicology (QST)
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

DILI is a primary cause of acute liver failure and reason for the termination of drug development programs...

Modeling and Simulation of Acetaminophen Pharmacokinetics and Hepatic Biomarkers After Overdoses of Extended-Release and Immediate-Release Formulations with DILIsym, a Quantitative Systems Toxicology (QST) Software Platform

Modeling and Simulation of Acetaminophen Pharmacokinetics and Hepatic Biomarkers After Overdoses of Extended-Release and Immediate-Release Formulations with DILIsym, a Quantitative Systems Toxicology (QST) Software Platform

Authors: Howell BA, Yang K, Beaudoin J, Lakhani VV, Woodhead JL, Lai JCK, Gelotte CK, Atillasoy E, Sista S
Conference: SOT
Keywords: acetaminophen, DILIsym, hepatic biomarker, modeling and simulation, overdose, pharmacokinetics, QST, Quantitative Systems Toxicology (QST)
Software: DILIsym®, GastroPlus®
Division: Quantitative Systems Pharmacology (QSP)

The analgesic/antipyretic acetaminophen (APAP) has multiple formulations including immediate-, modified-, and extended-release preparations...

Drug-like Properties of Serial Phenanthroindolizidine Alkaloid Compounds: ADMET Characteristic Prediction and Validation

Drug-like Properties of Serial Phenanthroindolizidine Alkaloid Compounds: ADMET Characteristic Prediction and Validation

Authors: Wang H, Hu J, Ji M, Wang R, Jin J, Ye J, Zhang H, Li L, Wang R, Yang Y, Gao Y, Xia X, Xu X, Gao L, Liu Y
Publication: Acta Materia Medica
Keywords: adme prediction, admet predictor, ADMET-risk, lead selection, machine learning, QSAR, virtual screening
Software: ADMET Predictor®
Division: Cheminformatics

Phenanthroindolizidine alkaloids (PAs) are a series of compounds that have been isolated from traditional herbal medicines and have significant therapeutic potential, such as anti-arthritic, anti-viral, anti-inflammatory, and anti-glioma effects in vitro and in vivo.

A Novel Stability-Indicating RP-HPLC Method for the Simultaneous Estimation and In Vitro and In vivo Evaluation: Curcumin and Naringin Co-amorphous System

A Novel Stability-Indicating RP-HPLC Method for the Simultaneous Estimation and In Vitro and In vivo Evaluation: Curcumin and Naringin Co-amorphous System

Authors: Mallya P, Yarlagadda DL, Lewis S
Publication: Food Anal Methods
Keywords: compartmental pharmacokinetics, gastroplus, nca, non-compartmental pharmacokinetics
Software: GastroPlus®

Curcumin (CUR) is a phytochemical widely used in food industries, cosmetics, and in the treatment of various ailments. It is a polyphenol derived from turmeric and is often considered the golden spice.

Screening inhibitors against the Ef-Tu of Fusobacterium nucleatum: a docking, ADMET and PBPK assessment study

Screening inhibitors against the Ef-Tu of Fusobacterium nucleatum: a docking, ADMET and PBPK assessment study

Authors: Alzamami A, Alturki NA, Khan K, Basharat Z, Mashraqi MM
Publication: Mol Divers
Keywords: gastroplus, high throughput pharmacokinetics, lead selection, library screening, machine learning, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

The oral pathogen Fusobacterium nucleatum has recently been associated with an elevated risk of colorectal cancer (CRC), endometrial metastasis, chemoresistance, inflammation, metastasis, and DNA damage, along with several other diseases.

Physiologically Based Pharmacokinetic Modeling for Confirming the Role of CYP3A1/2 and P-glycoprotein in Detoxification Mechanism Between Glycyrrhizic Acid and aconitine in Rats

Physiologically Based Pharmacokinetic Modeling for Confirming the Role of CYP3A1/2 and P-glycoprotein in Detoxification Mechanism Between Glycyrrhizic Acid and aconitine in Rats

Authors: Jin J, Xu X, Li F, Weng F, Zou B, Li Y, Zhao J, Zhang S, Yan D, Qiu F
Publication: J Appl Toxicol
Keywords: cyp 3a1/2, gastroplus, nonlinear pk, p-gp, pbbm, PBPK modeling, physiologically based pharmacokinetics, transporters
Software: GastroPlus®
Division: PBPK

Fuzi, an effective common herb, is often combined with Gancao to treat disease in clinical practice with enhancing its efficacy and alleviating its toxicity.

Prediction of Human Pharmacokinetics of E0703, a Novel Radioprotective Agent, Using Physiologically Based Pharmacokinetic Modeling and an Interspecies Extrapolation Approach

Prediction of Human Pharmacokinetics of E0703, a Novel Radioprotective Agent, Using Physiologically Based Pharmacokinetic Modeling and an Interspecies Extrapolation Approach

Authors: Ge YX, Zhang Z, Yan JY, Ma ZC, Wang YG, Xiao CR, Zhuang XM, Gao Y
Publication: Int J Mol Sciences
Keywords: animal scaling, dose selection, fih, first-in-human, gastroplus, in vitro–in vivo extrapolation, IVIVE, PBPK modeling, physiologically based pharmacokinetics, translational science
Software: GastroPlus®

E0703, a new steroidal compound optimized from estradiol, significantly increased cell proliferation and the survival rate of KM mice and beagles after ionizing radiation.

Discovery of TRPA1 Antagonist GDC-6599: Derisking Preclinical Toxicity and Aldehyde Oxidase Metabolism with a Potential First-in-Class Therapy for Respiratory Disease

Discovery of TRPA1 Antagonist GDC-6599: Derisking Preclinical Toxicity and Aldehyde Oxidase Metabolism with a Potential First-in-Class Therapy for Respiratory Disease

Authors: Terrett JA, Ly JQ, Katavolos P, Hasselgren C, Laing S, Zhong F, Villemure E, Déry M, Larouche-Gauthier R, Chen H, Shore DG, Lee WP, Suto E, Johnson K, Brooks M, Stablein A, Beaumier F, Constantineau-Forget L, Grand-Maître C, Lépissier L, Ciblat S, Sturino C, Chen Y, Hu B, Elstrott J, Gandham V, Joseph V, Booler H, Cain G, Chou C, Fullerton A, Lepherd M, Stainton S, Torres E, Urban K, Yu L, Zhong Y, Bao L, Chou KJ, Lin J, Zhang W, La H, Liu L, Mulder T, Chen J, Chernov-Rogan T, Johnson AR, Hackos DH, Leahey R, Shields SD, Balestrini A, Riol-Blanco L, Safina BS, Volgraf M, Magnuson S, Kakiuchi-Kiyota S
Publication: J Med Chem
Keywords: animal scaling, dose selection, fih, first-in-human, gastroplus, in vitro–in vivo extrapolation, IVIVE, PBPK modeling, physiologically based pharmacokinetics, translational science
Software: GastroPlus®

Transient receptor potential ankyrin 1 (TRPA1) is a nonselective calcium ion channel highly expressed in the primary sensory neurons, functioning as a polymodal sensor for exogenous and endogenous stimuli, and has been implicated in neuropathic pain and respiratory disease.

Regulatory Requirements and Applications of Physiologically Based Pharmacokinetic Models

Regulatory Requirements and Applications of Physiologically Based Pharmacokinetic Models

Authors: Cuquerella-Gilabert M, Garcia-Arieta A, Mangas-Sanjuán V, Reig López J
Publication: ADME Processes in Pharmaceutical Sciences
Keywords: drug pharmacokinetics, European Medicines Agency (EMA), PBPK modeling, U.S. Food and Drug Administration (FDA)

Physiologically based pharmacokinetic (PBPK) models have become a key tool to reduce the uncertainty and assure the best benefit-risk decisions in a model-informed drug discovery and development process.

Pharmacokinetic Simulation Study: Exploring the Impact of Clinical Parameters on Lamotrigine for Different Patient Populations with Implications for Liver Function Assessment and Therapeutic Drug Monitoring

Pharmacokinetic Simulation Study: Exploring the Impact of Clinical Parameters on Lamotrigine for Different Patient Populations with Implications for Liver Function Assessment and Therapeutic Drug Monitoring

Authors: Costa B, Silva I, Oliveira JC, Reguengo H, Vale N
Publication: Scientia Pharmaceutica
Keywords: DILIsym, disease populations, gastroplus, hepatic impairment, liver safety, PBPK modeling, physiologically based pharmacokinetics, QST, systems toxicology
Software: DILIsym®, GastroPlus®

Lamotrigine, widely used for managing epilepsy and bipolar disorder, carries potential side effects, including severe anticonvulsant hypersensitivity syndrome (AHS) or drug rash with eosinophilia and systemic symptoms (DRESS), which may lead to hepatotoxicity.