To quantitatively and mechanistically compare the liver toxicity potential of oral riluzole versus BHV-0223, combining clinical and mechanistic data, using DILIsym.
A Model-Based Approach to Bridging Plasma and Dried Blood Spot Concentration Data for Phase 3 Verubecestat Trials
Dried blood spot (DBS) pharmacokinetic (PK) sampling was investigated as a potential alternative to plasma sampling for Phase 3 verubecestat (MK-8931) trials due to several potential advantages (ie, reduced cost, reduced clinical site burden, and lower blood volume requirements)
Development of a Physiologically Based Pharmacokinetic Model for Losartan and Its Active Metabolite E3174 – Ethnic Differences in Pharmacokinetics between Caucasian and Asian Populations
Losartan is a selective, competitive angiotensin 11 receptor type 1 (AT1) antagonist for hypertension treatment.
Quantitative Systems Toxicology Modeling Using DILIsym Suggests That Mitochondrial Biogenesis Could Explain Adaptation to Drug-Induced Liver Injury (DILI)
Resolution of elevations of the liver injury biomarker serum ALT despite continued drug dosing, termed “adaptation”, is commonly observed in clinical trials, but the underlying mechanisms behind this phenomenon remain unclear.
Representation of Crizotinib and Pazopanib-mediated Drug-Induced Liver Injury (DILI) Using Quantitative Systems Toxicology (QST)
Crizotinib and pazopanib are oral receptor tyrosine kinase inhibitors (TKIs).
Concentration-QT Analysis of Quizartinib in Patients With Relapsed/Refractory AML
FMS-like tyrosine kinase 3 (FLT3) is expressed in hematopoietic progenitor cells, and signaling through FLT3 promotes these cells’ proliferation and differentiation.
Zonal Extracellular Matrix (ECM) Accumulation in Nonalcoholic Steatohepatitis (NASH) Characterized by a Mathematical Model of Fibrosis
Non-alcoholic fatty liver disease (NAFLD) is of growing concern, within developed countries, with recent estimates suggesting up to, 30% of the US population may be affected.
Bringing physiologically-based pharmacokinetic (PBPK) simulation to early drug discovery and development
Lack of efficacy continues to be a problem in drug development. Piecemeal rules of thumb such as Lipinski’s Rule of Five [1] help avoid compounds likely to be poorly...
in vitro to in vivo Extrapolation (IVIVE) of Itraconazole Precipitation Using A Biphasic Dissolution Test and Mechanistic Absorption Model
Regulatory agencies have encouraged the use of mechanistic absorption (MAM) and physiologically-based pharmacokinetic (PBPK) modeling to reduce both costs and time to market for new and generic drug products.
Verubecestat pharmacokinetic and exposure-response results from APECS, a phase 3 trial in prodromal alzheimer’s disease
The BACE inhibitor verubecestat (MK-8931) demonstrated cognitive and functional decline relative to placebo in a 2-year Phase 3 trial of individuals with prodromal AD (APECS; NCT01953601), along with reductions in brain volume and amyloid plaque. Disease progression modeling has demonstrated a lack of dose or exposure dependency in the clinical cognition and function endpoints (see Poster# P1-044)
Relationship Between Fremanezumab Exposure and Efficacy in Preventive Therapy of Chronic Migraine in Adults
Fremanezumab is a fully humanized IgG2Δa/kappa monoclonal antibody that selectively targets calcitonin gene-related peptide (CGRP).
Relationship Between Fremanezumab Exposure and Efficacy in Preventive Therapy of Episodic Migraine in Adults
Fremanezumab is a fully humanized IgG2Δa/kappa monoclonal antibody that selectively targets calcitonin gene-related peptide (CGRP).
Lack of Relationship Between Fremanezumab Exposure and Cardiovascular Adverse Events in Phase 2 and Phase 3 Data Including Chronic and Episodic Migraine Patients
Fremanezumab is a fully humanized IgG2Δa/kappa monoclonal antibody that selectively targets calcitonin gene-related peptide (CGRP). Previously, fremanezumab was found to be effective and…
Absence of Association Between Drug Exposure and Infection in Patients With Polyarticular-Course Juvenile Idiopathic Arthritis and Inadequate Response to Biologic or Non-Biologic DMARDs Treated With SC and IV Abatacept
Compared with adults, children are more susceptible to infections. In paediatric patients with juvenile idiopathic arthritis (JIA), infections are the most commonly reported AEs linked to biologic (b)DMARDs.
Population Pharmacokinetic Modeling of Fremanezumab in Support of Phase 3 Development for Patients with Migraine
Calcitonin gene-related protein (CGRP) is a well-studied neuropeptide that plays an important role in the pathophysiology of migraines, both centrally and peripherally.1,2 Jugular levels of CGRP are increased...
Data Exploration Libraries in KIWI
The cloud-based KIWI™ platform is an enterprise-scale application supporting the execution, management, and communication of modeling and simulation activities. Exploration of analysis datasets and model…
Data Repository to Enable Organization and Collaboration for Pharmacometric Analysis
Interdisciplinary research teams encounter both logistical and technical challenges during collaborative pharmacometric analyses projects, especially teams with significant geographic distributions.
Population Pharmacokinetics, Exposure-Efficacy, and Target Attainment Analyses of Tedizolid in Japanese and Chinese Subjects
Methicillin-resistant Staphylococcus aureus (MRSA) remains a threat for healthcare systems globally.1 MRSA frequently causes healthcare-associated infections and is associated with increased morbidity…
The Influence of Dissolution, PMAT Influx, and MATE Efflux Rates on Paracellular Absorption of Metformin Using a Mechanistic Oral Absorption / PBPK Model
A physiologically based absorption and distribution model was developed for metformin to facilitate our understanding of the influence of transporters and dissolution rate on oral absorption.
Abatacept Population Pharmacokinetics and Exposure-Response Analyses for Dose Recommendation of SC and IV Abatacept in Patients With Psoriatic Arthritis
Both subcutaneous (SC) and intravenous (IV) abatacept, a selective T-cell co-stimulation modulator, are approved for the treatment of adults with moderately to severely active rheumatoid arthritis (RA) and...