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...
Cosmetics Europe Evaluation of 6 in silico Skin Penetration Models
The Cosmetics Europe (CosEche) ADME Task Force aims to evaluate and develop in silico skin penetration models using relevant measured values.
Mechanistic Modeling Of Mitochondrial Biogenesis Within Dilisym Could Explain Clinically Observed Adaptation Of Serum Alanine Aminotransferase Elevations
Resolution of serum ALT elevations despite continued drug dosing, termed “adaptation”, is commonly observed in clinical trials, but the underlying mechanisms behind this phenomenon remain unclear.
Prediction of the Liver Toxicity of the Endothelin Receptor Antagonists Sitaxsentan and Ambrisentan for the Treatment of Pulmonary Arterial Hypertension with a Quantitative Systems Toxicology Tool (DILIsym)
Sitaxsentan and ambrisentan are highly selective endothelin-1 type A receptor antagonists which were developed for the treatment of pulmonary arterial hypertension.
Cognitive Engineering – The Tools, Mindset, and Strategy for an Integrated Development Standard
Internet technology facilitates connectedness but often fails to foster collaboration. Advanced modeling techniques can provide insight for development discussions, but in many cases, these tools…
Pharmacokinetic Analysis of Gatilfoxacin in Plasma and Sinus Aspirate Drug Treatment of Maxiliary Sinusitis
A novel approach to collect sinus exudate was utilized and the time course of gatifloxacin (GAT) in the blood and at the primary infection site were assessed during treatment for acute maxillary sinusitis (AMS).
Pharmacokinetics And Exposure-Response Relationships Of Dasotraline In The Treatment Of Attention-Deficit/Hyperactivity Disorder In Adults
To characterize the pharmacokinetic and pharmacodynamic data to explore the time course and exposure response relationships in Phase 2 to define dasotraline benefit to risk relationship in adult Attention...
Characterization of Population Pharmacokinetics of Cariprazine and Its Major Metabolites
Population pharmacokinetic (PK) analysis was undertaken to describe the concentration‑time profiles of cariprazine and its 2 major metabolites of similar pharmacological activity, desmethyl‑cariprazine...
IVIVC using in silico and PBPK methods for inhaled drug product development
The physiologically based model of the lung included in GastroPlus™ was used to simulate the absorption, distribution, and pharmacokinetics of two APIs from an inhaled combination product.