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Intérêt des outils d’investigation des enzymes métaboliques en pratique clinique

Investigation tools for metabolic enzymes in clinical practice

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Douleur et Analgésie

Résumé

La variabilité interindividuelle dans la réponse médicamenteuse est un problème clinique majeur. La polymédication et les polymorphismes génétiques modulant l’activité des enzymes du métabolisme médicamenteux tels que les cytochromes P450 (CYP) sont une source de variabilité dans la réponse médicamenteuse. De nouvelles techniques diagnostiques rendues plus sûres et plus simples à réaliser ont été développées afin de diagnostiquer les variations dans l’activité métabolique des CYP (tests de phénotypage) ou de rechercher des variantes alléliques spécifiques (génotypage). Alors que le génotypage des CYP offre la possibilité de prédire le phénotype en fonction des allèles identifiés pour autant que le lien entre génotype et phénotype soit établi, le phénotypage apporte des informations sur l’activité réelle (in vivo) des CYP et est le reflet d’une combinaison de facteurs génétiques, environnementaux et endogènes. Le génotypage et le phénotypage pourraient ainsi être considérés de manière prospective afin d’identifier la molécule idéale ou la dose adéquate à administrer chez un patient donné, ou de manière rétrospective pour expliquer une réponse médicamenteuse anormale (toxicité ou inefficacité).

Abstract

Interindividual variability in drug response is a major clinical issue. Polymedication and genetic polymorphism modulating the activity of drug metabolism enzymes such as cytochrome P450 (CYP) are a source of variability in the drug response. New diagnostic techniques that are more reliable and simpler to perform have been developed in order to diagnose the variations in metabolic activity of CYP (phenotyping tests) or to assess specific allelic variants (genotyping). While CYP genotyping gives the option to predict the phenotype based on the identified alleles, provided that the link between the genotype and the phenotype is established, phenotyping provides information on true (in vivo) CYP activity and is a reflection of a combination of genetic, environmental and endogenic factors. Thus, genotyping and phenotyping could be considered prospectively in order to identify the ideal molecule or the correct dose to administer to a given patient, or retrospectively to explain an abnormal drug response (toxicity or inefficacy).

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Authors and Affiliations

  1. Service de pharmacologie et toxicologie cliniques, hôpitaux universitaires de Genève, rue Gabrielle-Perret-Gentil-4, CH-1211, Genève, Suisse

    C. F. Samer, V. Rollason, K. Ing Lorenzini, Y. Daali & J. A. Desmeules

  2. Centre suisse de toxicologie humaine appliquée (SCAHT), université de Genève, Genève, Suisse

    C. F. Samer, Y. Daali & J. A. Desmeules

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  1. C. F. Samer
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  2. V. Rollason
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  3. K. Ing Lorenzini
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Correspondence to C. F. Samer.

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Samer, C.F., Rollason, V., Lorenzini, K.I. et al. Intérêt des outils d’investigation des enzymes métaboliques en pratique clinique. Douleur analg 26, 241–247 (2013). https://doi.org/10.1007/s11724-013-0354-8

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  • DOI: https://doi.org/10.1007/s11724-013-0354-8

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