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: DILIsym Services

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: DILIsym Services

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

Prediction of the Liver Safety Profile of a First-in-Class Myeloperoxidase Inhibitor Using Quantitative Systems Toxicology Modeling

Prediction of the Liver Safety Profile of a First-in-Class Myeloperoxidase Inhibitor Using Quantitative Systems Toxicology Modeling

Authors: Woodhead JL, Gebremichael Y, Macwan J, Qureshi IA, Bertz R, Wertz V, Howell BA
Conference: SOT
Keywords: bile acid transporters, DILIsym, liver enzymes, liver safety, liver toxicity, machine learning PBPK QST(P) marriage, mitochondrial function, MITOsym, neurodegenerative disease, neuroinflammatory disease, PBPK, Quantitative Systems Toxicology (QST), SimPops, verdiperstat
Software: DILIsym®, MITOsym®
Division: DILIsym Services

The novel myeloperoxidase inhibitor verdiperstat was developed as a treatment for...

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: DILIsym Services

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: Cognigen

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...

In Silico Analyses of a Promising Drug Candidate for the Treatment of Amyotrophic Lateral Sclerosis Targeting Superoxide Dismutase I Protein

In Silico Analyses of a Promising Drug Candidate for the Treatment of Amyotrophic Lateral Sclerosis Targeting Superoxide Dismutase I Protein

Authors: Pereira GRC, Abrahim-Vieira BA, de Mesquita JF
Publication: Pharmaceutics
Keywords: Amyotrophic lateral sclerosis (ALS), neurodegenerative disorder, pharmacokinetics, toxicological assessments
Software: ADMET Predictor®

Amyotrophic lateral sclerosis (ALS) is the most prevalent motor neuron disorder in adults, which is associated with a highly disabling condition

Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions

Preferential Solvation Study of Rosuvastatin in the {PEG400 (1) + Water (2)} Cosolvent Mixture and GastroPlus Software-Based In Vivo Predictions

Authors: Hussain A, Afzal O, Yasmin S, Haider N, Altamimi ASA, Martinez F, Acree Jr. WE, Ramzan M
Publication: ACS Omega
Keywords: biopharmaceutics, gastroplus, pbbm, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Rosuvastatin (RST) is a poorly water-soluble drug responsible for limited in vivo dissolution and subsequently low oral systemic absorption (poor bioavailability).