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.

Using forest plots to interpret covariate effects in pharmacometric models
AbstractThe inclusion of covariates in pharmacometric models is important due to their ability to explain variability in drug exposure and response. Clear communication of the impact of covariates is needed to support informed decision making in clinical practice and in drug development. However, effectively conveying these effects to key stakeholders and decision makers can be challenging. Forest plots have been proposed to meet these communication needs. However, forest plots for the illustration of covariate effects in pharmacometrics are complex combinations of model predictions, uncertainty estimates, tabulated result...
Source: CPT: Pharmacometrics and Systems Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Authors: E. Niclas Jonsson, Joakim Nyberg Tags: TUTORIAL Source Type: research

A systematic efficacy analysis of tuberculosis treatment with BPaL ‐containing regimens using a multiscale modeling approach
In this study, we present a unique framework that uses a primate granuloma modeling approach to screen many combination regimens that are currently under clinical and experimental exploration and assesses their efficacies to inform future studies. We tested well-studied regimens such as HRZE and BPaL to evaluate the validity and accuracy of our framework. We also simulated additional promising combination regimens that have not been sufficiently studied clinically or experimentally, and we provide a pipeline for regimen ranking based on their efficacies in granulomas. Furthermore, we showed a correlation between simulation...
Source: CPT: Pharmacometrics and Systems Pharmacology - February 26, 2024 Category: Drugs & Pharmacology Authors: Maral Budak, Laura E. Via, Danielle M. Weiner, Clifton E. Barry III, Pariksheet Nanda, Gabrielle Michael, Khisimuzi Mdluli, Denise Kirschner Tags: ARTICLE Source Type: research

Quantitative modeling of tumor dynamics and development of drug resistance in non ‐small cell lung cancer patients treated with erlotinib
This study aims to characterize the tumor dynamics and development of drug resistance in patients with non-small cell lung cancer treated with erlotinib, and investigate the relationship between baseline circulating tumor DNA (ctDNA) data and tumor dynamics. Data obtained for the analysis included (1) intensively sampled erlotinib concentrations from 29 patients from two previous pharmacokinetic (PK) studies, and (2) tumor sizes, ctDNA measurements, and sparsely sampled erlotinib concentrations from 18 patients from the START-TKI study. A two-compartment population PK model was first developed which well-described the PK d...
Source: CPT: Pharmacometrics and Systems Pharmacology - February 20, 2024 Category: Drugs & Pharmacology Authors: Anyue Yin, G. D. Marijn Veerman, Johan G. C. van Hasselt, Christi M. J. Steendam, Hendrikus Jan Dubbink, Henk ‐Jan Guchelaar, Lena E. Friberg, Anne‐Marie C. Dingemans, Ron H. J. Mathijssen, Dirk Jan A. R. Moes Tags: ARTICLE Source Type: research

Data ‐driven disease progression model of Parkinson's disease and effect of sex and genetic variants
In conclusion, a long-term PD progression model was successfully constructed using SReFT from relatively short-term individual patient observations and depicted nonlinear changes in relevant biomarkers and their covariates, including sex and ge netic variants. (Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - February 19, 2024 Category: Drugs & Pharmacology Authors: Ryota Jin, Hideki Yoshioka, Hiromi Sato, Akihiro Hisaka Tags: ARTICLE Source Type: research

Population pharmacokinetics of the GIP/GLP receptor agonist tirzepatide
AbstractTirzepatide is a first-in-class glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved as for the treatment of type 2 diabetes mellitus. A population-based pharmacokinetic (PK) model was developed from 19 pooled studies. Tirzepatide pharmacokinetics were well-described by a two-compartment model with first order absorption and elimination. The tirzepatide population PK model utilized a semimechanistic allometry model to describe the relationship between body size and tirzepatide PK. The half-life of tirzepatide was ~5  days and enabled sustained exposure with once-weekl...
Source: CPT: Pharmacometrics and Systems Pharmacology - February 15, 2024 Category: Drugs & Pharmacology Authors: Karen Schneck, Shweta Urva Tags: ARTICLE Source Type: research

In silico modeling and simulation of organ ‐on‐a‐chip systems to support data analysis and a priori experimental design
AbstractOrgan-on-a-chip (OoC) systems are a promising new class of in  vitro devices that can combine various tissues, cultured in different compartments, linked by media flow. The properties of these novel in vitro systems linked to increased physiological relevance of culture conditions may lead to more in vivo-relevant cell phenotypes, enabling better in vitro pharmacology and toxicology assessment. Improved cell activities combined with longer lasting cultures offer opportunities to improve the characterization of absorption, distribution, metabolism, and excretion (ADME) processes, potentially leading to more accu...
Source: CPT: Pharmacometrics and Systems Pharmacology - February 15, 2024 Category: Drugs & Pharmacology Authors: Nicol ó Milani, Neil Parrott, Aleksandra Galetin, Stephen Fowler, Michael Gertz Tags: TUTORIAL Source Type: research

Issue Information
(Source: CPT: Pharmacometrics and Systems Pharmacology)
Source: CPT: Pharmacometrics and Systems Pharmacology - February 14, 2024 Category: Drugs & Pharmacology Tags: ISSUE INFORMATION Source Type: research

Use of physiologically ‐based pharmacokinetic modeling to understand the effect of omeprazole administration on the pharmacokinetics of oral extended‐release nifedipine
This study used physiologically-based pharmacokinetic (PBPK ) modeling and simulations to investigate the underlying mechanism of these complex DDIs. A formulation exhibiting differences in in vitro dissolution across physiological pH range and another formulation where pH does not impact dissolution appreciably (e.g., an osmotic pump) were chosen to charac terize the potential impact of pH. The PBPK models incorporated two-stage in vitro release profiles via US Pharmacopeia 2 apparatus. PBPK simulations suggest that the elevated gastric pH following multiple-dose administration of omeprazole has a minimal effect on nife...
Source: CPT: Pharmacometrics and Systems Pharmacology - February 14, 2024 Category: Drugs & Pharmacology Authors: Ming ‐Liang Tan, Zongming Gao, Andrew Babiskin, Myong‐Jin Kim, Lanyan Fang, Lei Zhang, Liang Zhao Tags: ARTICLE Source Type: research