Idiosyncratic drug-induced liver injury (iDILI), which is typically rare and often severe, has led to black box warnings or drug withdrawals from the market...
Advancing Calcitonin Gene-Related Peptide Receptor Antagonists Using Quantitative Systems Toxicology Modeling to Characterize Next-in-Class Compounds Compared to the Hepatotoxic First in Class Telcagepant
While CGRP receptor antagonists have demonstrated efficacy in the acute and preventive treatment of migraine...
Simulx – GUI: a flexible and user-friendly application for simulations
Advanced simulator of clinical trials and decision-making tool
Quantitative Systems Toxicology Modeling Supports Safety Determination for Ubrogepant, a Novel CGRP Inhibitor
CGRP inhibitors are a class of drugs that meet a significant unmet medical need for migraine treatments.
Representation of Efavirenz mediated Drug Induced Liver Injury (DILI) Using Quantitative Systems Toxicology (QST)
Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in combination with other agents to treat human...
Mathematically modeling CD8+ T cell-mediated drug induced liver injury (DILI): from ovalbumin to amodiaquine in mice
Idiosyncratic drug-induced liver injury (iDILI) is poorlynunderstood, but there is evidence to support that some iDILI events may be immune-mediated.
Simulation of first-in-human using an allometrically scaled population mechanistic TMDD model with preclinical monkey data
First-in-human: what dose to choose to elicit the desired effect (efficacy), without causing harm (safety)?
Implementation of the C-QTc study using MonolixSuite applications
International Council for Harmonisation (ICH) E14 guidance agreed to use a model-based study of concentration-QT data as a primary analysis in...
A library of tumor growth and tumor growth inhibition models for the MonolixSuite
Modular tumor growth (TG) and tumor growth inhibition (TGI) library
Comparison of pharmacokinetics and QTc effect of Quizartinib in Japanese and non-Japanese patients with Relapsed/Refractory (R/R) FLT3-ITD positive acute myeloid leukemia (AML) using population pharmacokinetic (PopPK) analyses
The PopPK and C-QTc analyses were conducted to compare the pharmacokinetic (PK) profiles and QTc effect of quizartinib in Japanese...
Quantitative Prediction of Cisplatin-Induced Acute Kidney Injury Using RENAsym, a Mechanistic Quantitative Systems Toxicology Model, and Renal Proximal Tubule Epithelial Cell In vitro Assays
Nephrotoxic drugs like cisplatin cause acute kidney injury (AKI) through complex cellular mechanisms that include mitochondrial dysfunction...
Quantitative Systems Toxicology Modeling Using DILIsym Suggests That Drug-Induced Liver Injury Can Be Enhanced by Co-administered Drugs and Mitigated by Mitochondrial Biogenesis
Drug-induced liver injury (DILI) can be enhanced by polypharmacy if co-administered drugs induce toxicity via mechanisms that have overlapping pathways.
Exposure-Response Modeling From the CLARITY Trial of Pimavanserin for Adjunctive Treatment of Major Depressive Disorder
Pimavanserin displays selective inverse agonist and antagonist activity at 5-hydroxytryptamine-2A (5-HT2A) receptors with lesser activity at 5-HT2C receptors, and no appreciable activity at adrenergic, dopaminergic, histaminergic, or muscarinic receptors.
Pediatric dose selection for fremanezumab (AJOVY) phase 3 migraine study using pharmacokinetic data from a pediatric phase 1 study and a population pharmacokinetic modeling and simulation approach
Previous examination of the relationship between fremanezumab exposures and baseline body weight supports a weight cutoff of 45 kg of pediatric dose selection, with the approved adult dose of 225 mg monthly being appropriate or patients weighing >= 45 kg
Exposure–Response Analyses to Support Optimal Dosing Regimens of Ceftolozane/Tazobactam in Patients With Hospital-Acquired Pneumonia (HAP)/Ventilator-Associated Pneumonia (VAP) in ASPECT-NP
Nosocomial pneumonia comprises hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) and is the most common nosocomial infection; mortality rates range from 3%–22% for nonventilated HAP (10%–40% for ventilated HAP) and from 6%–29% for VAP.
Probability of Target Attainment Analyses to Inform Ceftolozane/Tazobactam Dosing Regimens in Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia Patients With End-Stage Renal Disease on Intermittent Hemodialysis
Nosocomial pneumonia, including hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), is a common type of hospital-acquired infection, with mortality rates estimated to be as high as 50%.
Ceftolozane/Tazobactam Probability of Target Attainment in Patients With Hospital-Acquired Pneumonia/ Ventilator-Associated Pneumonia
Hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) are common hospital-acquired infections that are associated with mortality rates as high as 50%
Stochastic Assessment of Adaptive Volunteer Infection Study (aVIS) Designs in Malaria – A Case Study with Artefenomel
Traditional Malaria Volunteer infection studies use three consecutive single dose level cohorts (n=8).
Development and Evaluation of a Simulation Platform for Malaria Volunteer Infection Study (VIS) Designs
Traditional malaria volunteer infection studies have three consecutive single-dose cohorts.
Generalized PBPK Model for Evaluation of Inhalation Exposure of Volatile Organic Compounds
Physiologically based pharmacokinetic modeling (PBPK) is a valuable tool to evaluate inhalation exposure of volatile organic compounds (VOCs).