학술논문

Circulating Biomarkers Instead of Genotyping to Establish Metabolizer Phenotypes.
Document Type
Article
Source
Annual Review of Pharmacology & Toxicology. Jan2024, Vol. 64, p65-87. 19p.
Subject
*PREVENTION of drug side effects
*BIOMARKERS
*PHARMACOGENOMICS
*EXOSOMES
*ARTIFICIAL intelligence
*INDIVIDUALIZED medicine
*GENOTYPES
*PREDICTION models
*PHENOTYPES
*DOSE-response relationship in biochemistry
*DOSAGE forms of drugs
Language
ISSN
0362-1642
Abstract
Pharmacogenomics (PGx) enables personalized treatment for the prediction of drug response and to avoid adverse drug reactions. Currently, PGx mainly relies on the genetic information of absorption, distribution, metabolism, and excretion (ADME) targets such as drug-metabolizing enzymes or transporters to predict differences in the patient's phenotype. However, there is evidence that the phenotype-genotype concordance is limited. Thus, we discuss different phenotyping strategies using exogenous xenobiotics (e.g., drug cocktails) or endogenous compounds for phenotype prediction. In particular, minimally invasive approaches focusing on liquid biopsies offer great potential to preemptively determine metabolic and transport capacities. Early studies indicate that ADME phenotyping using exosomes released from the liver is reliable. In addition, pharmacometric modeling and artificial intelligence improve phenotype prediction. However, further prospective studies are needed to demonstrate the clinical utility of individualized treatment based on phenotyping strategies, not only relying on genetics. The present review summarizes current knowledge and limitations. [ABSTRACT FROM AUTHOR]