en
Privat-docent thesis
English

Cytochromes P450 activity and functionality: biomarker of drug response and valuable tool for Precision Medicine

Defense date2017
Abstract

The variations in the activity and functionality of drug metabolizing enzymes and in particular cytochromes P450 (CYP) are major determinants of drug therapeutic outcomes as they impact on drug pharmacokinetics. This thesis aims to describe the crucial role of integrative methods assessing the impact of genetic and environmental factors on CYP activity to support safe and effective drug therapies and more broadly precision medicine. After an outline on precision medicine and its major component pharmacogenomics, the characteristics of CYPs and importance in the field are described. In vitro, in vivo, and in silico methods allowing studying drug metabolism and CYP activity are then presented, and in particular the Geneva cocktail for CYP phenotyping developed and validated in our laboratory. Applications for clinical research and clinical pharmacology are then exemplified by the centenary opioid oxycodone whose pharmacokinetics and pharmacodynamics were reappraised using in vitro, in vivo and in silico technologies. Our findings led to clinical recommendations fully applicable to precision medicine. Finally, we review the current evidence on the clinical impact of CYP activity variations from genetic and environmental origins on drug response, and in particular clinical applications of CYP testing in pain medicine and other relevant medical specialties.

eng
Keywords
  • Cytochromes P450
  • Precision Medicine
  • Personalized Medicine
  • Oxycodone
  • Phenotyping
  • Genotyping
  • PBPK modeling
Citation (ISO format)
SAMER, Caroline Flora. Cytochromes P450 activity and functionality: biomarker of drug response and valuable tool for Precision Medicine. 2017. doi: 10.13097/archive-ouverte/unige:94125
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Technical informations

Creation05/10/2017 9:46:00 AM
First validation05/10/2017 9:46:00 AM
Update time03/15/2023 1:39:54 AM
Status update03/15/2023 1:39:54 AM
Last indexation01/29/2024 9:05:09 PM
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