1.176 hasil
Menampilkan 1–20 · 0,24 detik · RSS
CPT: Pharmacometrics & Systems Pharmacology
Scopus
ISSN 2163-8306 · Wiley · 1.176 artikel di indeks
-
Artikel Jurnal
Pharmacometric‐Based Evaluation of Salmeterol and Its Metabolite α‐Hydroxysalmeterol in Plasma and Urine: Practical Implications for Doping Control
ABSTRACT Salmeterol is a commonly used β2‐agonist included on the List of Prohibited Substances and Methods published by the World Anti‐Doping Agency (WADA). We developed a population pharmacokinetic (popPK) model to describe the PK of salmeterol including its major metabolite, α‐hydroxysalmeterol…
-
Artikel Jurnal
Population Physiologically‐Based Pharmacokinetic Modeling to Determine Ontogeny: A Quantitative Clinical Pharmacology Example in Pediatric Rare Disease
ABSTRACT Pediatric physiologically‐based pharmacokinetic (PBPK) modelling plays an increasing role in selecting doses in children and addressing clinical pharmacology questions. Ethical concerns often limit clinical pharmacology studies that have no direct therapeutic benefit in children…
-
Artikel Jurnal
Examining the Reliability of Model‐Based Meta‐Analysis (MBMA) Outcomes: A Simulation Study
ABSTRACT Model‐based meta‐analysis (MBMA) can be utilized to synthesize literature data and predict drug efficacy, particularly suitable for constructing external comparator arms for non‐randomized controlled trials (NRCTs). This study evaluated the reliability of MBMA by comparing covariate models…
-
Artikel Jurnal
Combining Aggregate Data and Individual Patient Data in Model‐Based Meta‐Analysis: An Illustrative Case Study of Tofacitinib in Rheumatoid Arthritis Patients
ABSTRACT Model‐based meta‐analysis (MBMA) utilizes aggregate data (AD) and allows integration of information from multiple studies, which may provide more statistical power to detect clinically relevant treatment effects than an individual randomized controlled trial alone. Access to individual…
-
Artikel Jurnal
A Quantitative Systems Pharmacology (QSP) Model of Acute Hepatitis B Virus Infection: Mechanistic Insights and Foundations for Future Extensions
ABSTRACT Chronic hepatitis B virus (HBV) infection remains a significant global health challenge. While the dynamic interplay between viral replication and host immune responses determines infection outcomes, the mechanisms driving the resolution of acute infection versus the emergence of…
-
Artikel Jurnal
Development of a Physiologically Based Model of Bilirubin Metabolism in Health and Disease and Its Comparison With Real‐World Data
ABSTRACT Bilirubin is a breakdown product of erythrocytes and plays a crucial role in elimination of heme‐containing proteins. After its synthesis in the reticuloendothelial system, unconjugated bilirubin is released into plasma and taken up into the liver. In hepatocytes, bilirubin is conjugated…
-
Artikel Jurnal
Evaluating Model‐Based Extrapolation of Plasma Exposure for Long‐Acting Injectable Products: From Single‐ to Multiple‐Dose Trials
ABSTRACT Long‐acting injectable medicinal products (LAIs) prolong drug release and thereby aim to enhance adherence and patient outcomes. European regulatory guidelines require the conduct of single‐ and multiple‐dose trials to exclude differences in drug release between non‐steady and steady state…
-
Artikel Jurnal
A QSP Model of Valproic Acid Toxicity in Pediatric and Adult Populations: Implications for Formulation Selection and L‐Carnitine Supplementation
ABSTRACT Valproic acid (VPA), a widely prescribed short‐chain fatty acid for managing epilepsy, psychiatric conditions, and migraines, offers significant therapeutic benefits despite its concerning toxicity profile. This study extends our previously developed Quantitative Systems Pharmacology (QSP)…
-
Artikel Jurnal
Anti‐PD‐(L)1 Antibodies: Insights From QSP‐Based Meta‐Analysis
ABSTRACT Checkpoint inhibitors that target PD‐1 or PD‐L1 have had a profound effect in a variety of cancers, both as a single therapy and in combinations. Meta‐analyses suggest that monoclonal antibodies (mAbs) targeting PD‐1 may yield better survival outcomes compared to anti‐PD‐L1 mAbs, however…
-
Artikel Jurnal
Latent Variable Indirect Response Modeling of Cendakimab Exposure–Response for Longitudinal Dysphagia Days Using a Combined Uniform‐Binomial Likelihood Framework
ABSTRACT To characterize the relationship between cendakimab exposure and the longitudinal efficacy endpoint dysphagia days (DD), E–R analyses were performed using data from the EE‐001 study (N = 427) with eosinophilic esophagitis. DD—a bounded, discrete endpoint assessed over 14‐day period via…
-
Artikel Jurnal
Tackling High Dimensionality in QSP: Guiding Model Order Reduction With Index Analysis
ABSTRACT Quantitative systems pharmacology (QSP) models offer a useful platform to integrate drug pharmacology with knowledge about biological mechanisms across multiple scales and data sources into a unified quantitative framework. This makes them invaluable to address many relevant questions in…
-
Artikel Jurnal
Population Pharmacokinetic/Pharmacodynamic Modeling of Donidalorsen, an Antisense Oligonucleotide in Development for Prophylaxis of Hereditary Angioedema
ABSTRACT Hereditary angioedema (HAE) is a rare disorder linked to kallikrein‐kinin system dysregulation, which leads to uncontrolled activation of plasma prekallikrein. Donidalorsen is an antisense oligonucleotide designed to selectively degrade prekallikrein messenger RNA and thereby reduce…
-
Artikel Jurnal
Immunogenicity Publication Bias and Its Consequences for Predictive Models: A Call for Transparent Reporting
ABSTRACT Understanding immunogenicity is crucial to improving therapeutic protein development. By comparing Phase I to III antidrug antibody (ADA) incidence data of Roche‐internal and approved monoclonal antibodies, we demonstrate a bias toward lower ADA incidence in published data, partly because…
-
Artikel Jurnal
Tutorial on Causal Mediation Analysis for Pharmacometricians
ABSTRACT Mediation analyses can support biomarker development by quantifying the part of the total treatment effect on clinical outcome that is mediated by the biomarker. Given that pharmacometricians are often involved in the analysis of biomarker data with pharmacokinetic–pharmacodynamic (PK–PD)…
-
Artikel Jurnal
Model‐Based Meta‐Analysis With MonolixSuite: A Tutorial for Longitudinal Categorical and Continuous Data
ABSTRACT Model‐based meta‐analysis (MBMA) informs key drug development decisions by integrating data, published or unpublished, from multiple studies. Due to these various sources of information and the use of summary‐level data (e.g., mean responses over treatment arms or percent responders), MBMA…
-
Artikel Jurnal
Mathematical Modeling of the Role of Cytokines in Sindbis Virus Treatment of Glioblastoma
ABSTRACT Oncolytic viruses, specifically Sindbis virus (SINV), combined with cytokines show promising results in slowing glioma progression, but a quantitative understanding of their effects remains limited. In this study, we use an ordinary differential equation (ODE) model to examine the effect…
-
Artikel Jurnal
Beyond the Michaelis–Menten: Evaluation of a tQSSA‐Based IVIVE Approach for Predicting In Vivo Intrinsic Clearance From Hepatocyte Assays
ABSTRACT The classical Michaelis–Menten model, under the standard quasi‐steady‐state approximation (sQSSA), is widely used in in vitro‐in vivo extrapolation (IVIVE) studies using hepatocyte or human liver microsomal (HLM) assays to predict intrinsic hepatic clearance (Clint,vitro). However, the…
-
Artikel Jurnal
Integrating MBMA and QSP to Identify Key Covariates and Predict Treatment Outcomes in Relapsed/Refractory Multiple Myeloma
ABSTRACT This study demonstrates the application of a model based meta analysis (MBMA) framework to characterize the safety and efficacy profiles of therapies in relapsed and refractory multiple myeloma (RRMM). Published clinical trial data were analyzed to evaluate the incidence of Grade ≥ 3…
-
Artikel Jurnal
Novel Drug‐Disease Modeling Framework for Oncology Benefit–Risk Evaluation: Application to Tusamitamab Ravtansine
ABSTRACT This study introduces a novel drug‐disease modeling framework designed to assess the benefit–risk balance of antibody‐drug conjugates (ADC) in oncology. The framework integrates dose levels, pharmacokinetics, tumor growth dynamics, progression‐free survival (PFS), and dose‐adjusted adverse…
-
Artikel Jurnal
Establishing Immune Correlates of Protection Against Respiratory Syncytial Virus Infection to Accelerate Vaccine Development: A Model‐Based Meta‐Analysis
ABSTRACT The objectives of this study were to quantify the relationship between vaccine‐induced immunogenicity responses and the protection against respiratory syncytial virus (RSV) infection‐related clinical outcomes, and to evaluate immunogenicity as a surrogate marker for vaccine efficacy (VE)…
Menampilkan maksimal 50 halaman. Persempit pencarian dengan filter untuk hasil yang lebih spesifik.