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Clinical Pharmacokinetics

, Volume 58, Issue 12, pp 1517–1532 | Cite as

Towards Personalized Antithrombotic Treatments: Focus on P2Y12 Inhibitors and Direct Oral Anticoagulants

  • Jean Terrier
  • Youssef Daali
  • Pierre Fontana
  • Chantal Csajka
  • Jean-Luc RenyEmail author
Review Article
  • 113 Downloads

Abstract

Oral anticoagulants and antiplatelet drugs are commonly prescribed to lower the risk of cardiovascular diseases, such as venous and arterial thrombosis, which represent the leading causes of mortality worldwide. A significant percentage of patients taking antithrombotics will nevertheless experience bleeding or recurrent ischemic events, and this represents a major public health issue. Cardiovascular medicine is now questioning the one-size-fits-all policy, and more personalized approaches are increasingly being considered. However, the available tools are currently limited and they are only moderately able to predict clinical events or have a significant impact on clinical outcomes. Predicting concentrations of antithrombotics in blood could be an effective means of personalization as they have been associated with bleeding and recurrent ischemia. Target concentration interventions could take advantage of physiologically based pharmacokinetic (PBPK) and population-based pharmacokinetic (POPPK) models, which are increasingly used in clinical settings and have attracted the interest of governmental regulatory agencies, to propose dosages adapted to specific population characteristics. These models have the benefit of combining parameters from different sources, such as experimental in vitro data and patients’ demographic, genetic, and physiological in vivo data, to characterize the dose–concentration relationships of compounds of interest. As such, they can be used to predict individual drug exposure. In the near future, these models could therefore be a valuable means of predicting personalized antithrombotic blood concentrations and, hopefully, of preventing clinical non-response or bleeding in a given patient. Existing approaches for personalization of antithrombotic prescriptions will be reviewed using practical examples for P2Y12 inhibitors and direct oral anticoagulants. The review will additionally focus on the existing PBPK and POPPK models for these two categories of drugs. Lastly, we address potential scenarios for their implementation in clinics, along with the main limitations and challenges.

Notes

Acknowledgements

This work was performed within the framework of the Swiss National Science Foundation’s PNR74 Project 407440_167381 on the ‘Automated detection of adverse drug events from older inpatients’ electronic medical records using structured data’.

Compliance with Ethical Standards

Funding

No external funding was used in the preparation of this manuscript.

Conflict of interest

Jean Terrier, Youssef Daali, Pierre Fontana, Chantal Csajka, and Jean-Luc Reny declare that they have no potential conflicts of interest that may be relevant to the contents of this manuscript.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of General Internal MedicineGeneva University HospitalsGenevaSwitzerland
  2. 2.Geneva Platelet Group, Faculty of MedicineUniversity of GenevaGenevaSwitzerland
  3. 3.School of Pharmaceutical SciencesUniversity of Geneva, University of LausanneGenevaSwitzerland
  4. 4.Clinical Pharmacology and Toxicology Service, Anesthesiology, Pharmacology and Intensive Care DepartmentGeneva University HospitalsGenevaSwitzerland
  5. 5.Division of Angiology and HaemostasisGeneva University HospitalsGenevaSwitzerland
  6. 6.Division of Internal Medicine and RehabilitationGeneva University HospitalsGenevaSwitzerland

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