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.

Multistate modeling for survival analysis in critically ill patients treated with meropenem
This study investigated predictors of in-hospital mortality in critically ill patients treated with meropenem by pharmacometric multistate modeling. A multistate model compris ing five states (ongoing meropenem treatment, other antibiotic treatment, antibiotic treatment termination, discharge, and death) was developed to capture the transitions in a cohort of 577 critically ill patients treated with meropenem. Various factors were investigated as potential predictors of t he transitions, including patient demographics, creatinine clearance calculated by Cockcroft–Gault equation (CLCRCG), time that unbound concentrations ...
Source: CPT: Pharmacometrics and Systems Pharmacology - November 7, 2023 Category: Drugs & Pharmacology Authors: Yaru Peng, Iris K. Minichmayr, Han Liu, Feifan Xie, Lena E. Friberg Tags: ARTICLE Source Type: research

Quantitative modeling of approved and emerging therapeutics for modifying TTR levels in patients with Transthyretin Amyloid Cardiomyopathy
This study exemplifies how modeling can be used to compare modalities with differing mechanisms of action. (Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - November 7, 2023 Category: Drugs & Pharmacology Authors: Kimiko McGirr, Saheli Sarkar, Kalyanasundaram Subramanian Tags: ARTICLE Source Type: research

Pediatric model ‐based dose optimization using a pooled exposure–response safety analysis for nivolumab and nivolumab plus ipilimumab combination in melanoma
AbstractAn exposure –response (E–R) safety analysis was conducted across adult and pediatric (<18  years) studies to evaluate the potential impact of higher nivolumab and/or ipilimumab exposures in adolescents (≥12 to<18  years) versus adults with melanoma using the approved adult dosing regimens for nivolumab alone or in combination with ipilimumab. Data from 3507 patients across 15 studies were used to examine the relationship between nivolumab–ipilimumab daily average exposure and time to grade 2+ immune-medi ated adverse events (gr2+ IMAEs). Results from the E–R safety model showed ipilimumab, but n...
Source: CPT: Pharmacometrics and Systems Pharmacology - November 6, 2023 Category: Drugs & Pharmacology Authors: Shengnan Du, Yue Zhao, Zheyi Hu, Sihang Liu, Amit Roy, Jun Shen, Li Zhu, Lora Hamuro Tags: ARTICLE Source Type: research

Adult and pediatric physiologically ‐based biopharmaceutics modeling to explain lamotrigine immediate release absorption process.
AbstractPhysiologically-based biopharmaceutics modeling (PBBM) has potential to accelerate the development of new drug and formulations. An important application of PBBM is for special populations such as pediatrics that have pharmacokinetics (PK) dependent on the maturation process. Lamotrigine (LTG) is a BCS II drug and is widely prescribed. Therefore, the goal of this study was to assess the biopharmaceutics risk of the low-soluble drug LTG when the ontogeny on gastrointestinal tract (GIT) physiological parameters are considered. An oral physiologically-based pharmacokinetic (PBPK) model and a PBBM were developed and ve...
Source: CPT: Pharmacometrics and Systems Pharmacology - November 3, 2023 Category: Drugs & Pharmacology Authors: Edilainy Rizzieri Caleffi ‐Marchesini, Amanda Antunes Herling, Julia Macente, Rodolfo Hernandes Bonan, Priscila de Freitas Lima, Rafaela Moreno, Veriano Alexandre, Nitin Bharat Charbe, Fernanda Belincanta Borghi‐Pangoni, Rodrigo Cristofoletti Tags: ARTICLE Source Type: research

Application of the model ‐informed drug development paradigm to datopotamab deruxtecan dose selection for late‐stage development
AbstractTo replace the conventional maximum tolerated dose (MTD) approach, a paradigm for dose optimization and dose selection that relies on model-informed drug development (MIDD) approaches has been proposed in oncology. Here, we report our application of an MIDD approach during phase I to inform dose selection for the late-stage development of datopotamab deruxtecan (Dato-DXd). Dato-DXd is a TROP2-directed antibody-drug conjugate being developed for advanced/metastatic non-small cell lung cancer (NSCLC) and other tumors. Data on pharmacokinetics (PKs), efficacy, and safety in NSCLC were collected in the TROPION-PanTumor...
Source: CPT: Pharmacometrics and Systems Pharmacology - November 2, 2023 Category: Drugs & Pharmacology Authors: Yasong Lu, Shuang Liang, Ying Hong, Naoyuki Tajima, Kashyap Patel, Hanbin Li, David R. Wada, Jon Greenberg, Adam Petrich, Hong Zebger ‐Gong, Dale Shuster, Pavan Vaddady Tags: CASE REPORT Source Type: research

A convolution ‐based in vitro‐in vivo correlation model for methylphenidate hydrochloride delayed‐release and extended‐release capsule
AbstractDelayed-release and extended-release methylphenidate hydrochloride (JORNAY PM ®) is a novel capsule formulation of methylphenidate hydrochloride, used to treat attention deficit hyperactivity disorder in patients 6 years and older. In this paper, we develop a Level A in vitro-in vivo correlation (IVIVC) model for extended-release methylphenidate hydrochloride to support p ost-approval manufacturing changes by evaluating a point-to-point correlation between the fraction of drug dissolved in vitro and the fraction of drug absorbed in vivo. Dissolution data from an in vitro study of three different release form...
Source: CPT: Pharmacometrics and Systems Pharmacology - November 1, 2023 Category: Drugs & Pharmacology Authors: Pawan Kumar Gupta, Bev Incledon, Jogarao V. S. Gobburu, Roberto Gomeni Tags: ARTICLE Source Type: research

Bridging population pharmacokinetic and semimechanistic absorption modeling of APX3330
This study describes the pharmacokinetics of APX3330 and explores effect of food on absorption. Total plasma quinone concentrations of APX3330 were obtained following oral administration from studies in healthy Japanese male subjects (single dose-escalation; multiple-dose; food-effect) and patients with cancer patients. Nonlinear mixed effects modeling was performed using Monolix to estimate pharmacokinetic parameters and assess covariate effects. To further evaluate the effect of food on absorption, a semi-physiologic pharmacokinetic model was developed in Gastroplus to delineate effects of food on dissolution and absorpt...
Source: CPT: Pharmacometrics and Systems Pharmacology - October 27, 2023 Category: Drugs & Pharmacology Authors: Larissa L. Silva, Robert E. Stratford, Richard Messmann, Mark R. Kelley, Sara K. Quinney Tags: ARTICLE Source Type: research

Multistate modeling for survival analysis in critically ill patients treated with meropenem
This study investigated predictors of in-hospital mortality in critically ill patients treated with meropenem by pharmacometric multistate modeling. A multistate model comprising five states (ongoing meropenem treatment, other antibiotic treatment, antibiotic treatment termination, discharge, and death) was developed to capture the transitions in a cohort of 577 critically ill patients treated with meropenem. Various factors were investigated as potential predictors of the transitions, including patient demographics, CLCRCG (creatinine clearance calculated by Cockcroft –Gault equation),fT>MIC (time that unbound concen...
Source: CPT: Pharmacometrics and Systems Pharmacology - October 26, 2023 Category: Drugs & Pharmacology Authors: Yaru Peng, Iris K. Minichmayr, Han Liu, Feifan Xie, Lena E. Friberg Tags: ARTICLE Source Type: research

Comparison of two ‐stage and joint TGI‐OS modeling using data from six atezolizumab clinical studies in patients with metastatic non‐small cell lung cancer
AbstractTwo-stage and joint modeling approaches are the two main approaches to investigate the link between longitudinal tumor size data and overall survival (OS) and anticipate clinical trial outcome. We here used a large database composed of one phase II and five phase III clinical trials evaluating atezolizumab (an immunotherapy) in monotherapy or in combination with chemotherapies in 3699 patients with non-small cell lung cancer to evaluate the differences between both approaches in terms of parameter estimates, magnitude of covariate effects, and ability to predict OS. Although the two-stage approach may underestimate...
Source: CPT: Pharmacometrics and Systems Pharmacology - October 25, 2023 Category: Drugs & Pharmacology Authors: Antonio Gon çalves, Mathilde Marchand, Phyllis Chan, Jin Y. Jin, Jérémie Guedj, René Bruno Tags: ARTICLE Source Type: research