Laura Villain, Mariana Guimaraes Sa Correia, Sophie Fischer-Holzhausen, Alexander Kulesza, Stephan Schaller, Marco Siccardi
ESQlabs GmbH
Objectives:
Multiple factors can complicate the optimization of drug dosing for populations of patients. The combination of patient characteristics, disease states, and concomitant therapies can affect drug absorption, distribution, metabolism, and elimination. Effects on pharmacokinetics can compromise efficacy and toxicity, generating unique scenarios that cannot be investigated through traditional clinical studies. Predictive computational platforms provide a framework to rationalize the selection of suitable dosing strategies for patients. The objective of this abstract is to provide a comprehensive review and description of simulation strategies across diseases, populations, and polypharmacy scenarios using PK-sim and Mobi. Options provided by the OSP Suite software describing existing models for populations will be illustrated with specific examples to explore scenarios related to women’s health.
Methods:
A comprehensive software and literature review was conducted to identify OSP suite solutions and existing models developed and verified/qualified with OSP suite solutions applicable to special populations. A search in PubMed, targeting models developed using the OSP suite and special populations identified 107 relevant entries, including reviews and original articles (status February 2024). Additionally, a snowball sampling approach was performed to include any further relevant articles mentioned in the initial review articles, complying with the focus of the search. Models were categorized depending on the level of verification for describing their accuracy and reliability (verified with clinical data in special populations or a priori prediction). Subsequently, verified models were classified according to the specific population included in the simulations, such as pregnant women, elderly individuals, or patients with specific diseases. A special focus was placed on understanding the current capabilities and literature status for the application of the OSP suite software tools to predict the impact of various stages of women’s health and life journey, including stages such as contraception, pregnancy, or lactation. Finally, models were categorized based on dosing strategy and applications, to identify the most common administration routes (e.g., oral, dermal, intravenous) and context of use (e.g. oral absorption formulation design, drug-drug interactions risk assessment).
Results:
The literature review showed that 42 models have gone through extended qualification workflows, defined by demonstrated agreement with clinical data and supporting the quantitative prediction of different clinical scenarios. These studies belonging to this class can be used to formulate good practices for the sharing of models for credible re-use, and further expansions to new populations or compound scenarios can be implemented.
As for the thematic focus of this review – women’s health – 10 verified models were found for contraception methods, pregnancy, and lactation, demonstrating that PK-sim and Mobi can be applied to gain valuable insights for individualization of drug therapy across different stages of a woman’s life.
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Conclusions:
This work highlights the potential of OSP suite software to optimize drug therapy across diverse populations and specific “life development journeys” like the one presented for women’s health. Integrating validated and verified models with population-specific and compound-specific data can inform safer and more effective dosing strategies for vulnerable groups, ultimately leading to stratified and personalized medicine approaches.
References:
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[2] Text for reference 2, etc etc
Reference: PAGE 32 (2024) Abstr 11116 [www.page-meeting.org/?abstract=11116]
Poster: Methodology - Other topics