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.
Modeling of Active Transport and Metabolism for Hepatocyte Assays with Application of In Vitro to In Vivo Extrapolation (IVIVE)
Sandwich and suspended hepatocyte cultures are routinely used to assess either active transport and/or metabolism of drug molecules.
Development of In Vitro-In Vivo Correlation for Long Acting Injectable Microsphere Formulations
The concept of in vitro-in vivo correlations (IVIVCs) for long-acting injectable (LAI) microsphere formulations has gained more significance in the past decade.
Application of Physiologically Based Pharmacokinetic (PBPK) Models in Predicting Drug Pharmacokinetics for Different Ethnic Groups
The purpose of this study was to evaluate the ability of PBPK models to predict the pharmacokinects (PK) of different compounds in two ethnic groups, Caucasian and Chinese.
Robust Uncertainty Estimates for Unbalanced Data Sets
Mathematical models of quantitative structure-activity relationships (QSARs) play a key role in qualifying synthesis ideas, drug candidates and leads.
Population Pharmacokinetics (PK) and Exposure-Efficacy Analyses of Nivolumab in Subjects with Advanced Hepatocellular Carcinoma (HCC)
Nivolumab is a fully human immunoglobulin G4 (IgG4) monoclonal antibody (mAb) that selectively binds to the programmed death-1 (PD-1) membrane receptor. PD-1 is a negative regulatory molecule expressed...
Population Pharmacokinetics and Exposure-Response Analyses for Abatacept in Juvenile Idiopathic Arthritis
Polyarticular-course juvenile idiopathic arthritis (pJIA) is the most common chronic rheumatic disorder in children and one of the leading causes of childhood-acquired disability. Treatment with biologic...
Systemization of Time-to-Event Analyses for Pharmacometric Applications
In addition to the values of efficacy and safety endpoints, the timing of such endpoints relative to the start of treatment is often of interest. A commonly used statistical methodology for analyzing such...