CPT: Pharmacometrics and Systems Pharmacology This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Clinical pharmacokinetics of leriglitazone and a translational approach using PBPK modeling to guide the selection of the starting dose in children
AbstractLeriglitazone is a unique peroxisome proliferator-activated receptor-gamma (PPAR γ) agonist that crosses the blood–brain barrier in humans and clinical trials have shown evidence of efficacy in neurodegenerative diseases. At clinical doses which are well-tolerated, leriglitazone reaches the target central nervous system (CNS) concentrations that are needed for PPARγ engageme nt and efficacy; PPARγ engagement is also supported by clinical and anti-inflammatory biomarker changes in the Cerebrospinal fluid in the CNS. Plasma pharmacokinetics (PK) of leriglitazone were determined in a phase 1 study in male healthy...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 29, 2024 Category: Drugs & Pharmacology Authors: Estefania Traver, Laura Rodr íguez‐Pascau, Uwe Meya, Guillem Pina, Silvia Pascual, Sonia Poli, David Eckland, Jeroen van de Wetering, Alice Ke, Andreas Lindauer, Marc Martinell, Pilar Pizcueta Tags: ARTICLE Source Type: research

Population longitudinal analysis of Gait Profile Score and North Star Ambulatory Assessment in children with Duchenne muscular dystrophy
AbstractDuchenne muscular dystrophy (DMD) is a rare X-linked recessive disorder characterized by loss-of-function mutations in the gene encoding dystrophin. These mutations lead to progressive functional deterioration including muscle weakness, respiratory insufficiency, and musculoskeletal deformities. Three-dimensional gait analysis (3DGA) has been used as a tool to analyze gait pathology through the quantification of altered joint kinematics, kinetics, and muscle activity patterns. Among 3DGA indices, the Gait Profile Score (GPS), has been used as a sensitive overall measure to detect clinically relevant changes in gait...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 28, 2024 Category: Drugs & Pharmacology Authors: Jiexin Deng, Fangli Liu, Zhifen Feng, Zhigang Liu Tags: ARTICLE Source Type: research

Quantitative evaluation of trastuzumab deruxtecan pharmacokinetics and pharmacodynamics in mouse models of varying degrees of HER2 expression
AbstractTrastuzumab deruxtecan (T-DXd; DS-8201; ENHERTU ®) is a human epithelial growth factor receptor 2 (HER2)-directed antibody drug conjugate (ADC) with demonstrated antitumor activity against a range of tumor types. Aiming to understand the relationship between antigen expression and downstream efficacy outcomes, T-DXd was administered in tumor-bea ring mice carrying NCI-N87, Capan-1, JIMT-1, and MDA-MB-468 xenografts, characterized by varying HER2 levels. Plasma pharmacokinetics (PK) of total antibody, T-DXd, and released DXd and tumor concentrations of released DXd were evaluated, in addition to monitoring γΗ2AX ...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 27, 2024 Category: Drugs & Pharmacology Authors: Christina Vasalou, Theresa A. Proia, Laura Kazlauskas, Anna Przybyla, Matthew Sung, Srinivas Mamidi, Kim Maratea, Matthew Griffin, Rebecca Sargeant, Jelena Urosevic, Anton I. Rosenbaum, Jiaqi Yuan, Krishna C. Aluri, Diane Ramsden, Niresh Har Tags: ARTICLE Source Type: research

A population pharmacokinetic model using allometric scaling for baricitinib in patients with juvenile idiopathic arthritis
AbstractBaricitinib is approved for the treatment of rheumatoid arthritis (RA) in more than 70 countries, and juvenile idiopathic arthritis (JIA) in the European Union. Population pharmacokinetic (PK) models were developed in a phase 3 trial to characterize PK in pediatric patients with JIA and identify weight-based dosing regimens. The phase 3, randomized, double-blind, placebo-controlled withdrawal, efficacy and safety trial, JUVE-BASIS, enrolled patients (aged 2 to<18  years) with polyarticular course JIA. During a safety/PK period, baricitinib concentration data from age-based dose cohorts were compared to concent...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 27, 2024 Category: Drugs & Pharmacology Authors: Rodney L. Decker, C. Steven Ernest II, David B. Radtke, Rona Wang, Joana Ara újo, Stuart Y. Keller, Xin Zhang Tags: ARTICLE Source Type: research

Population pharmacokinetic ‐pharmacodynamic modeling of serum biomarkers as predictors of tumor dynamics following lenvatinib treatment in patients with radioiodine‐refractory differentiated thyroid cancer (RR‐DTC)
AbstractLenvatinib is a receptor tyrosine kinase (RTK) inhibitor targeting vascular endothelial growth factor (VEGF) receptors 1 –3, fibroblast growth factor (FGF) receptors 1–4, platelet-derived growth factor receptor-α (PDGFRα), KIT, and RET that have been implicated in pathogenic angiogenesis, tumor growth, and cancer. The primary objective of this work was to evaluate, by establishing quantitative relationships, whe ther lenvatinib exposure and longitudinal serum biomarker data (VEGF, Ang-2, Tie-2, and FGF-23) are predictors for change in longitudinal tumor size which was assessed based on data from 558 patients ...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Authors: Oneeb Majid, Seiichi Hayato, Sree Harsha Sreerama  Reddy, Bojan Lalovic, Taro Hihara, Taisuke Hoshi, Yasuhiro Funahashi, Jagadeesh Aluri, Osamu Takenaka, Sanae Yasuda, Ziad Hussein Tags: ARTICLE Source Type: research

Medication adherence framework: A population ‐based pharmacokinetic approach and its application in antimalarial treatment assessments
We reported here on the development of a pharmacometric framework to assess patient adherence, by using two population-based approaches – the percentile and the Bayesian method. Three different dosing strategies were investigated in patients prescribed a total of three doses; (1) non-observed therapy, (2) directly observed administration of the first dose, and (3) directly observed administration of the first two doses. The percen tile approach used population-based simulations to derive optimal concentration percentile cutoff values from the distribution of simulated drug concentrations at a specific time. This was done...
Source: CPT: Pharmacometrics and Systems Pharmacology - March 26, 2024 Category: Drugs & Pharmacology Authors: Junjie Ding, Richard M. Hoglund, Joel Tarning Tags: ARTICLE Source Type: research

Model ‐based meta‐analysis to quantify the effects of short interfering RNA therapeutics on hepatitis B surface antigen turnover in hepatitis B‐infected mice
In conclusion, non-clinical HBsAg concentration-time data after siRNA administration can be described using the presented KPD-IRM MBMA framework. This framework allows to quantitatively compare the effects of siRNAs on the HBsAg time course and inform dose and regimen selection across siRNA classes. These results may support siRNA development, optimize preclinical study designs, and inform data analysis methodology of future anti-HBV siRNAs; and ultimately, support siRNA model-informed drug development (MIDD) strategies. (Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - March 25, 2024 Category: Drugs & Pharmacology Authors: Louis Sandra, Huybrecht T'jollyn, An Vermeulen, Oliver Ackaert, Juan ‐Jose Perez‐Ruixo Tags: SYSTEMatIC REVIEW Source Type: research