Development of a Quantitative Systems Pharmacology (QSP) model is a long process with many iterative steps. Lack of standard practices for publishing QSP models has resulted in limited model reproducibility within the field. Multiple studies have identified that model reproducibility is a large challenge, especially for QSP models. This work aimed to investigate the causes of QSP model reproducibility issues and suggest standard practices as a potential solution to ensure QSP models are reproducible. In addition, a protocol is suggested as a guidance towards better publication strategy across journals, hoping to enable QSP knowledge preservation.
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http://dx.doi.org/10.1007/s10928-024-09943-6 | DOI Listing |
Handb Exp Pharmacol
January 2025
Genentech Inc, South San Francisco, CA, USA.
In this chapter, we envision the future of Quantitative Systems Pharmacology (QSP) which integrates closely with emerging data and technologies including advanced analytics, novel experimental technologies, and diverse and larger datasets. Machine learning (ML) and Artificial Intelligence (AI) will increasingly help QSP modelers to find, prepare, integrate, and exploit larger and diverse datasets, as well as build, parameterize, and simulate models. We picture QSP models being applied during all stages of drug discovery and development: During the discovery stages, QSP models predict the early human experience of in silico compounds created by generative AI.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
January 2025
Astellas Pharma Inc., Northbrook, Illinois, USA.
The antitumor efficacy of an intratumoral injection of a genetically engineered oncolytic vaccinia virus carrying human IL-7 and murine IL-12 genes (hIL-7/mIL-12-VV) was demonstrated in CT26.WT-bearing mice. In the CT26.
View Article and Find Full Text PDFPharmaceutics
December 2024
Department of Pharmacokinetics and Physical Pharmacy, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
Autoimmune diseases (AIDs) are a group of disorders in which the immune system attacks the body's own tissues, leading to chronic inflammation and organ damage. These diseases are difficult to treat due to variability in drug PK among individuals, patient responses to treatment, and the side effects of long-term immunosuppressive therapies. In recent years, pharmacometrics has emerged as a critical tool in drug discovery and development (DDD) and precision medicine.
View Article and Find Full Text PDFHandb Exp Pharmacol
December 2024
Rosa & Co, LLC, San Carlos, CA, USA.
Quantitative systems pharmacology (QSP) is a modeling approach employed in drug research and development that combines mechanistic representations of biological processes with drug pharmacology to deepen biological understanding and predict the responses to novel drugs or protocols. QSP has evolved from and is related to other modeling approaches, but has a number of unique attributes and applications. Here, we clarify the definition of QSP and its key features, trace its evolution, briefly compare it to other approaches, and explain why and how it can be used to reduce risk and improve efficiency in drug research and development.
View Article and Find Full Text PDFCPT Pharmacometrics Syst Pharmacol
December 2024
Department of Pharmaceutics and Brain Barriers Research Center, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Type 2 diabetes mellitus (T2DM), characterized by insulin resistance, is closely associated with Alzheimer's disease (AD). Cerebrovascular dysfunction is manifested in both T2DM and AD, and is often considered as a pathological link between the two diseases. Insulin signaling regulates critical functions of the blood-brain barrier (BBB), and endothelial insulin resistance could lead to BBB dysfunction, aggravating AD pathology.
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