About this Research Topic
Precision medicine is in constant progression in different aspects of patient care. It is a key part of patient management to optimize the safety and efficacy of the medication. Pharmacokinetics (PK), one of the principal sources of variability, is influenced by different factors including genetic polymorphisms, drug-drug interactions (DDI), and diseases. Metabolic enzymes including phase I and phase II enzymes and transporters are key factors in PK variability. The prediction of their activity and the identification of the main factors influencing their modulation at the individual level is primordial to optimize drug therapy.
Moreover, interactions between these factors lead to complex drug-drug-gene-disease interactions which are difficult to predict and to manage. Therefore, there is an urgent need to increase our knowledge regarding these sources of variability and, more importantly, how to translate this knowledge in the clinical setting.
Finally, model-based dose optimization tools using physiologically-based pharmacokinetic (PBPK) or population PK could be efficient for improving drug therapy since they have the potential to manage complex scenarios.
We are currently facing important challenges and needs:
• The current knowledge on the clinical impact of intrinsic factors (genetics, disease, etc.) on the magnitude of DDI is limited.
• Large clinical studies are needed to validate identified genetic polymorphisms involving both metabolic enzymes and transporters in clinical therapy.
• Complex gene-environment (including drugs and diseases) interactions need to be studied in clinical studies.
• Model-informed precision dosing needs to be developed and healthcare professionals need to be sensitized by increasing pregraduate and postgraduate teaching of these tools.
To respond to these challenges, in this Research Topic we welcome studies on the following subtopics:
• Update on genetic polymorphisms of metabolic enzymes and transporters, and their clinical implication in cardiovascular, oncology, infectiology, and psychiatry.
• Clinically pertinent studies involving enzymes and transporters drug-drug interactions.
• Complex drug-drug-gene interactions involving metabolic enzymes and transporters.
• Clinical impact of patient diseases (diabetes, organs failure, inflammation, among others) and genetic polymorphisms on the worsening of DDI magnitude.
• How could model-based dose optimization tools help to manage complex drug-drug-gene-disease interactions.
Please find more information on the Article Types guidelines in the Pharmacogenetics and Pharmacogenomics section here.
Topic Editor Professor Amin Rostami is the Senior Vice President of Research & Development and Chief Scientific Officer at Certara. All other Topic Editors declare no competing interests with regards to the Research Topic subject.
Keywords: precision medicine, cytochromes P450, drug transporters, pharmacogenomics, drug-drug interactions
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