Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays

Next generation risk assessment of human exposure to estrogens using safe comparator compound values based on in vitro bioactivity assays

Authors: van Tongeren TCA, Wang S, Carmichael PL, Rietjens IMCM, Li H
Publication: Regul Tox
Keywords: 3R compliant method, Dietary Comparator, Estrogen receptor, In vitro/in silico approaches, risk assessment
Software: ADMET Predictor®

In next generation risk assessment (NGRA), the Dietary Comparator Ratio (DCR) can be used to assess the safety of chemical exposures to humans in a 3R compliant approach.

Harmonizing Biopredictive Methodologies Through the Product Quality Research Institute (PQRI) Part I: Biopredictive Dissolution of Ibuprofen and Dipyridamole Tablets

Harmonizing Biopredictive Methodologies Through the Product Quality Research Institute (PQRI) Part I: Biopredictive Dissolution of Ibuprofen and Dipyridamole Tablets

Authors: Tsume Y, Ashworth L, Bermejo M, Cheng J, Cicale V, Dressman J, Fushimi M, González-Álvarez I, Guo Y, Jankovsky C, Lu X, Matsui K, Patel S, Sanderson N, Sun CC, Thakral NK, Yamane M, Zöller L
Publication: AAPS J
Keywords: biorelevant dissolution, gastroplus, IVIVC, ivivr, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: GastroPlus®

Assessing in vivo performance to inform formulation selection and development decisions is an important aspect of drug development.

Artificial Intelligence in Drug Metabolism and Excretion Prediction: Recent Advances, Challenges, and Future Perspectives

Artificial Intelligence in Drug Metabolism and Excretion Prediction: Recent Advances, Challenges, and Future Perspectives

Authors: Tran TTV, Tayara H, Chong KT
Publication: Pharmaceutics
Keywords: artificial intelligence, deep learning, drug discovery, drug excretion, drug metabolism, in silico method, machine learning, web servers
Software: ADMET Predictor®

Drug metabolism and excretion play crucial roles in determining the efficacy and safety of drug candidates, and predicting these processes is an essential part of drug discovery and development.

Enhancing Drug-Drug Interaction Prediction by Integrating Physiologically-Based Pharmacokinetic Model with Fraction Metabolized by CYP3A4

Enhancing Drug-Drug Interaction Prediction by Integrating Physiologically-Based Pharmacokinetic Model with Fraction Metabolized by CYP3A4

Authors: Jiang P, Chen T, Chu L, Xu R, Gao J, Wang L, Liu Q, Tang L, Wan H, Li M, Hong-can R
Publication: Authorea
Keywords: clinical pharmacology, ddI, drug–drug interaction, gastroplus, metabolism-based ddi, PBPK modeling
Software: GastroPlus®

Enhancing the precision of drug-drug interaction (DDI) prediction is essential for mitigating potential drug interactions and enhancing drug safety and efficacy.

Effect of Food and a Proton-Pump Inhibitor on the Absorption of Encorafenib: An In Vivo–In Vitro–In Silico Approach

Effect of Food and a Proton-Pump Inhibitor on the Absorption of Encorafenib: An In Vivo–In Vitro–In Silico Approach

Authors: Piscitelli J, Hens B, Tomaszewska I, Wollenberg L, Litwiler K, McAllister M, Reddy M
Publication: J Biomol Struct Dyn
Keywords: fih, first-in-human, gastroplus, IVIVE, pbbm, PBPK modeling, physiologically based pharmacokinetics, pulmonary playlist
Software: GastroPlus®

Encorafenib is a kinase inhibitor indicated for the treatment of patients with BRAF mutant melanoma and BRAF mutant metastatic colorectal cancer.

Quantitative Systems Toxicology (QST) Modeling Using DILIsym Informed Safe Dose Selection of Emvododstat in Acute Myeloid Leukemia (AML) Patients

Quantitative Systems Toxicology (QST) Modeling Using DILIsym Informed Safe Dose Selection of Emvododstat in Acute Myeloid Leukemia (AML) Patients

Authors: Yang K, Kong R, Maliakal P, Spiegel R, Baird JD, O’Keefe K, Watkins PB, Howell BA
Conference: ASCPT
Keywords: acute myeloid leukemia, ALT elevations, AML, anticancer, bile acid transport, clinical trials, desmethyl metabolite, DILIsym, dosing, emvododstat, hepatotoxicity, in vitro assays, in vivo exposure, liver safety, machine learning PBPK QST(P) marriage, mitochondrial function, oxidative stress, PBPK model, Quantitative Systems Toxicology (QST), SimPops
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Clinical investigation of emvododstat for the treatment of solid tumors was terminated after two patients who were heavily...

Development of a Quantitative Systems Toxicology Model of Multidrug Resistance Protein 3 (MDR3) Inhibition to Predict Bile Acid Mediated Cholestatic Drug Induced Liver Injury

Development of a Quantitative Systems Toxicology Model of Multidrug Resistance Protein 3 (MDR3) Inhibition to Predict Bile Acid Mediated Cholestatic Drug Induced Liver Injury

Authors: Beaudoin J, Yang K, Adiwidjaja J, Taneja G, Watkins PB, Siler SQ, Howell BA, Woodhead JL
Conference: SOT
Keywords: ambrisentan, bile acids, bile duct, bile duct injury, bile salt export pump (BSEP), biliary bicarbonate secretion, cholehepatic, cholestatic liver injury, DILIsym, drug induced liver injury (DILI), hepatocytes, hepatotoxicity, inhibition, MDR3, pioglitazone, shunting, SimPops
Software: DILIsym®
Division: Quantitative Systems Pharmacology (QSP)

Multidrug resistance protein 3 (MDR3) translocates phospholipids (PLs) from the inner to the outer leaflet of the canalicular...

Lunch & Learn – SOT 62nd Annual Meeting and ToxExpo

Lunch & Learn – SOT 62nd Annual Meeting and ToxExpo

Authors: Fohey J, Howell BA
Conference: SOT
Keywords: ADMET cheminformatics, CARDIOsym, DILIsym, gastroplus, GOUTsym, ILDsym, IPFsym, kidney safety, KIDNEYsym, liver safety, MITOsym, NAFLDsym, PBPK, pharmacometrics, Quantitative Systems Toxicology (QST), regulatory interaction, RENAsym, risk assessment, SimPops
Software: ADMET Predictor®, CARDIOsym, DILIsym®, GastroPlus®, ILDsym™, IPFsym®, KIDNEYsym, MITOsym®, NAFLDsym®, RENAsym®
Division: Quantitative Systems Pharmacology (QSP)

SOT 2023: Updates from Simulations Plus, Your Partner in Safety Assessment

Therapy with Allogeneic SARS-CoV-2-specific T-cells for Persistent COVID-19 in Immunocompromised Patients

Therapy with Allogeneic SARS-CoV-2-specific T-cells for Persistent COVID-19 in Immunocompromised Patients

Authors: Haidar G, Jacobs JL, Kramer KH, Naqvi A, Heaps AL, Parikh UM, McCormick KD, Sobolewski M, Agha M, Bogdanovich T, Bushunow V, Farah R, Hensley M, Hsu YMS, Johnson B, Klamar-Blain C, Kozar J, Lendermon E, Macatangay BJC, Marino CC, Raptis A, Salese E, Silveira FP, Leen AM, Marshall WL, Miller M, Patel B, Atillasoy E, Mellors JW
Publication: Clinical Infectious Diseases
Keywords: COVID-19, immunocompromised, prolonged infection, SARS-CoV-2, T-cell

We administered SARS-CoV-2 VST under emergency IND to 6 immunocompromised patients with persistent COVID-19 and characterized clinical and virologic responses: three patients had partial responses after failing other therapies but then died.

An integrated computational approach to infer therapeutic targets from Campylobacter concisus and peptidomimetic based inhibition of its pyrimidine metabolism pathway

An integrated computational approach to infer therapeutic targets from Campylobacter concisus and peptidomimetic based inhibition of its pyrimidine metabolism pathway

Authors: Khan K, Jalal K, Alam Y, Alotaibi G, Al Mouslem A, Uddin R, Hassan SS, Basharat Z
Publication: J Biomol Struct Dyn
Keywords: fih, first-in-human, gastroplus, IVIVE, pbbm, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Campylobacter concisus is a commensal of the human oral flora that has been allied with persistent diarrhea and inflammatory bowel disease (IBD).

Ceftolozane/Tazobactam Probability of Target Attainment in Patients With Hospital-Acquired Pneumonia/ Ventilator-Associated Pneumonia

Ceftolozane/Tazobactam Probability of Target Attainment in Patients With Hospital-Acquired Pneumonia/ Ventilator-Associated Pneumonia

Authors: Gao W, Patel YT, Zhang Z, Johnson MG, Fiedler-Kelly J, Bruno CJ, Rhee EG, De Anda C, Feng HP
Publication: Journal of Clinical Pharmacology
Keywords: antibacterial agent, ceftolozane, epithelial lining fluid, gram-negative bacterial infection, nosocomial pneumonia, probability of target attainment, renal insufficiency, tazobactam
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Probability of target attainment (PTA) analyses were conducted to support the recommended ceftolozane/tazobactam dosing regimens, adjusted for renal function, in patients with hospital-acquired/ventilator-associated...

Targeting Olokizumab-Interleukin 6 interaction interface to discover novel IL-6 inhibitors

Targeting Olokizumab-Interleukin 6 interaction interface to discover novel IL-6 inhibitors

Authors: Tran QH, Cao HN, Nguyen DN, Tran TTN, Le MT, Nguyen QT, Tran VH, Thai KM
Publication: J Biomol Struct Dyn
Keywords: Interleukin 6, molecular docking, molecular dynamic simulation, pharmacophore modeling, protein-protein interaction inhibitors
Software: ADMET Predictor®
Therapeutic Areas: Inflammation

The IL-6/IL-6R or IL-6/GP130 protein-protein interactions play a significant role in controlling the development of chronic inflammatory diseases, such as rheumatoid arthritis...