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An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
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Caracterización espaciotemporal de la sulfasalazina y la farmacocinética del 5-ASA utilizando un dispositivo de
Jingwei Cai1, Jordan S Mar1, Bennett Kapili2
1Genentech Inc., South San Francisco, California, USA.
Clinical pharmacology and therapeutics
|August 29, 2025
Resumen
Sulfasalazina y sus derivados
Área de la Ciencia:
- Farmacología
- Gastroenterología
- Investigación del microbioma
Sus antecedentes:
- La eficacia de la sulfasalazina en la enfermedad inflamatoria intestinal es variable debido a la farmacocinética compleja y al metabolismo microbiano específico del paciente.
- El muestreo preciso de la concentración de fármaco gastrointestinal es un reto, lo que dificulta la optimización del tratamiento con sulfasalazina.
- La azo-reducción bacteriana es crucial para la activación de la sulfasalazina en ácido 5-aminosalicílico (5-ASA).
Objetivo del estudio:
- Investigar la farmacocinética de la sulfasalazina, correlacionando las concentraciones intestinales y sistémicas del fármaco con la capacidad metabólica bacteriana.
- Evaluar la utilidad del dispositivo de muestreo luminal CapScan® para el análisis de la concentración de fármacos en regiones específicas.
- Comprender la distribución espacial de la sulfasalazina y sus metabolitos en el tracto gastrointestinal.
Principales métodos:
- 10 voluntarios sanos ingirieron sulfasalazina y dispositivos CapScan®.
- Se extrajeron muestras de CapScan® de las heces y se asignaron a localizaciones intestinales mediante perfiles metabólicos y metagenómicos.
- Se analizaron las concentraciones sistémicas y luminales del fármaco (sulfasalazina, 5-ASA, N-acetil-5-ASA) y la presencia de genes bacterianos.
Principales resultados:
- La sulfasalazina sistémica alcanzó su punto máximo a las 4 horas, mientras que el 5-ASA y el N-acetil-5-ASA alcanzaron su punto máximo a las 8 horas.
- La concentración de sulfasalazina fue más alta en el intestino delgado proximal (IS), disminuyendo distalmente a medida que aumentaba el 5-ASA y el N-acetil-5-ASA.
- Las concentraciones plasmáticas de 5-ASA se correlacionaron con las concentraciones distales de SI; se detectaron genes bacterianos de azorreductaza y acetiltransferasa en regiones gastrointestinales específicas.
Conclusiones:
- Se observaron concentraciones luminales espacialmente distintas de sulfasalazina y sus metabolitos.
- Existe una fuerte correlación entre los niveles distales de 5-ASA en el SI y la exposición plasmática temprana.
- El muestreo luminal tiene potencial para mejorar la comprensión de la farmacocinética del fármaco y optimizar las estrategias de administración oral del fármaco.
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