Title:In vivo Phenotyping Methods: Cytochrome P450 Probes with Emphasis on the Cocktail Approach
Volume: 23
Issue: 14
Author(s): Guillermo Alberto Keller*, María Laura Ferreirós Gago, Roberto Alejandro Diez and Guillermo Di Girolamo
Affiliation:
- Segunda Cátedra de Farmacología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 – Piso 16, C1121ABG Ciudad Autónoma de Buenos Aires,Argentina
Keywords:
Pharmacogenomics, phenotype, cytochrome P450, genotype, probe, cocktail, polymorphism.
Abstract: Background: Differences in drug response among patients are common. Most major drugs are effective
in only 25 to 60 percent of the patients, in part due to the CYP enzymes, whose activity vary up to 50-fold
between individuals for some index metabolic reactions. Several factors affect CYP activity, among which genetic
polymorphisms have been studied as the major cause for long time. Age, gender, disease states, and environmental
influences such as smoking, concomitant drug treatment or exposure to environmental chemicals are
also important.
Methods: This article reviews the available literature on multiple phenotypes assessment as an important tool to
predict possible therapeutic failures or toxic reactions to conventional drug doses during patient evaluation.
Results: Probe drugs can be used in various combinations allowing for the in vivo assessment of multiple pathways
of drug metabolism in a single experiment, configuring a new tool known as phenotyping "cocktails". There
are several drug cocktails with different advantages and disadvantages. Most of them have sufficient clinical
evidence and data validation to support their use in clinical setting as a surrogate for the risk of adverse reaction
in the course of therapy, leading to a better balance between efficacy and safety.
Conclusion: Probes characteristics and metabolic ratio measurements are important in the evaluation of phenotyping
cocktails as near-future applications.
