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Fenotipado farmaco-metabonómico y tratamiento personalizado de drogas
T Andrew Clayton1, John C Lindon, Olivier Cloarec
1Biological Chemistry, Biomedical Sciences Division, Faculty of Natural Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington, London SW7 2AZ, UK.
Nature
|April 21, 2006
Resumen
La terapia farmacológica personalizada se puede mejorar considerando los factores ambientales junto con la genética. Un nuevo enfoque farmaco-metabonómico utiliza el perfil de metabolitos para predecir las respuestas individuales a los medicamentos, mostrando una promesa de tratamientos más seguros y efectivos.
Área de la Ciencia:
- Farmacología Farmacología.
- La Metabolomía es una parte de la Metabolomía.
- La medicina personalizada es una medicina personalizada.
Sus antecedentes:
- Los tratamientos personalizados con fármacos requieren predecir las respuestas individuales a combinaciones específicas de fármacos y dosis.
- La farmacogenómica tiene limitaciones debido a pasar por alto las influencias ambientales en el metabolismo de los medicamentos.
- La variación de la respuesta interindividual al fármaco se ve significativamente afectada por el fenotipo metabólico, influenciado por la genética y los factores ambientales.
Objetivo del estudio:
- Introducir y validar un nuevo enfoque "farmaco-metabonómico" para la personalización del tratamiento de drogas.
- Demostrar la capacidad de predecir las respuestas individuales a los fármacos utilizando perfiles de metabolitos y quimiometría previos a la dosis.
- Evaluar la sensibilidad de este enfoque a las influencias genéticas y ambientales.
Principales métodos:
- Uso de perfiles de metabolitos antes de la dosis de los sujetos.
- Modelado quimiométrico aplicado para analizar datos de metabolitos y predecir respuestas a fármacos.
- Realizó un estudio de prueba de principio utilizando paracetamol (acetaminofén) en ratas.
Principales resultados:
- Se ha demostrado con éxito la predicción previa a la dosis de un componente del perfil del metabolito de un fármaco urinario.
- Se estableció una asociación entre la composición urinaria previa a la dosis y la gravedad del daño hepático inducido por el paracetamol.
- Mostró la sensibilidad del enfoque farmaco-metabonómico a los factores genéticos y ambientales.
Conclusiones:
- El enfoque farmaco-metabonómico ofrece una nueva estrategia para la personalización de la terapia farmacológica.
- Este método integra el perfil metabólico con la quimiometría para predecir las respuestas individuales a los medicamentos.
- Tiene el potencial de mejorar la eficacia del medicamento y reducir las reacciones adversas al tener en cuenta los factores holísticos del paciente.
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