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).
Quantitative Systems Toxicology (DILIsym) Modeling of the Acetaminophen Cellular Pathways for Liver Toxicity Supports that Acetaminophen is Not a Carcinogenic Hazard in Humans
Acetaminophen has a long history of safe use at therapeutic doses, but can cause liver injury at very high doses.
Synergy Between Two Mechanisms of Action Contributes to Species Differences in the Liver Safety Profile for PF-04895162
PF-04895162 (ICA-105665), a drug in development for the treatment of epilepsy, was terminated after transaminase elevations (up to grade...
Quantitative Systems Toxicology Modeling of Cisplatin Nephrotoxicity Using in vitro Assays of Proximal Tubule Epithelial Cells for Mechanistic Toxicity Pathways
Cisplatin-induced nephrotoxicity results in acute kidney injury (AKI) and is caused by various cellular mechanisms, including...
Using in silico-in vitro to in vivo Extrapolation (IS-IVIVE) to Predict the Oral Dose Required to Activate the Aryl Hydrocarbon Receptor (AhR)
Activation of AhR can have toxic effects on mammalian hosts
Mechanistic Modelling of the Linkage Between Proximal Tubule Cell Sublethal Injury and Tubular Sodium Reabsorption Impairment
Sublethal renal epithelial cell injury, a key manifestation of drug-induced acute kidney injury (AKI), is characterized by loss of brush border and cellular polarity of proximal tubular cells (PTCs).
Evaluating the Nephrotoxicity of Exemplar Compounds Using a Mechanistic Model of Drug-Induced Acute Kidney Injury
Drug-induced nephrotoxicity is a common source of acute kidney injury (AKI) and a condition that complicates clinical outcomes of vulnerable patients.
Mechanistic Modeling Aids in the Interpretation of Alanine Aminotransferase Elevations Associated with Clinical Ischemic Liver Injury
DILIsym® software can use serial serum alanine aminotransferase (ALT) assessments to predict hepatocyte loss (HL) and corresponding changes in total bilirubin (TBIL) due to...
Physiologically Based Pharmacokinetic Model for Voriconazole and Prediction of its Interactions with Midazolam and Alfentanil
Voriconazole (formerly known as UK-109,496), is a second-generation triazole antifungal agent widely used in the treatment of invasive fungal infections.
Exploring Clinical Relevance of Dissolution Testing by Physiologically Based Biopharmaceutics Modeling (PBBM)
In vitro dissolution testing, if reflective of in vivo drug release/absorption, is considered a surrogate for in vivo drug performance.
Predicting Shrinkage of Individual Parameters in More Complex NLME Models Using Bayesian Fisher Information Matrix
When data are sparse, parameters derived from a non-linear mixed effects model analysis...
Synergy Between Two Mechanisms of Action Contributes to Species Differences in the Liver Safety Profile for PF-04895162
The Purpose is to better understand the mechanisms underlying the apparent species differences, between rat and human, when evaluating the liver safety of compound PF-04895162.
Development of a Physiologically Based Pharmacokinetic (PBPK) Model for Intra-articular Delivery
Understanding local concentrations in intra-articular tissues and fluids such as cartilage, synovial membrane, and synovial fluid are a valuable tool to predict potential...
Efavirenz Physiologically Based Pharmacokinetic Model Development and Validation as a Moderate CYP3A4 Inducer for Drug-Drug Interaction Predictions
Efavirenz is an antiretroviral medication used to treat and prevent HIV/AIDS.