Category: 論文
Guide to development of compound files for PBPK modeling in the Simcyp population-based simulator
The Simcyp Simulator is a software platform for population physiologically-based pharmacokinetic (PBPK) modeling and simulation. It links in vitro data to in vivo absorption, distribution, metabolism, excretion and pharmacokinetic/pharmacodynamic outcomes to explore clinical scenarios and …
Real-world application of PBPK in drug discovery
The utility of PBPK models in support of drug development has been well documented. During the discovery stage, PBPK has increasingly been applied for early risk assessment, prediction of …
Physiologically Based Pharmacokinetic modelling of drugs in pregnancy: A mini-review on availability and limitations
This mini-review provides a concise and comprehensive overview of the pregnancy PBPK field and identify patterns and possible future directions in pregnancy PK research. Future applications are discussed from clinical, regulatory and industry perspective.
A Literature Review of Changes in Phase II Drug-Metabolizing Enzyme and Drug Transporter Expression during Pregnancy
This comprehensive review exposes gaps in current knowledge of phase II enzyme and drug transporter localization, expression, and regulation during pregnancy, which emphasizes the need for further research. The information collected will aid in optimizing pregnancy PBPK models to inform dose selection in pregnancy population.
Total and Free Blood and Plasma Concentration Changes in Pregnancy for Medicines Highly Bound to Plasma Proteins: Application of Physiologically Based Pharmacokinetic Modelling to Understand the Impact on Efficacy
For drugs highly bound to plasma proteins, changes in concentrations of free drug may have important implications for dose adjustment in pregnancy. The PBPK modelling can aid the understanding of the changes in drugs binding to plasma proteins and simulate free concentrations in pregnancy, providing support to inform dosing adjustment in this population.
A quantitative clinical pharmacology-based framework for model-informed vaccine development
Historically, vaccine development and dose optimization have followed mostly empirical approaches without clinical pharmacology and model-informed approaches playing a major role, in contrast to conventional drug development. This is attributed to the complex cascade of immunobiological mechanisms associated with …
No Recipe for Quantitative Systems Pharmacology Model Validation, but a Balancing Act Between Risk and Cost
Quantitative systems pharmacology (QSP) models generate predictions by formalizing biological understanding and integrating multiscale data, leading to beneficial extrapolation abilities, but may require careful balancing of the model’s scope with prediction uncertainties.
Analysis of clinical failure of anti-tau and anti-synuclein antibodies in neurodegeneration using a quantitative systems pharmacology model
Hugo Geerts, Silke Bergeler, Mike Walker, Piet van der Graaf, Jean-Philippe Courade. Sci Rep. 2023 Sep 1;13(1):1434
Development and Verification of a Japanese Pediatric Physiologically Based Pharmacokinetic Model with Emphasis on Drugs Eliminated by Cytochrome P450 or Renal Excretion
Physiologically based pharmacokinetic (PBPK) models are useful in bridging drug exposure in different ethnic groups, and there is increasing regulatory application of this approach in adults. Reported pediatric PBPK models tend to focus on the North European population, with few examples in other ethnic groups. This study describes the development and verification of a Japanese … Continued
