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Farmacocinética y distribución de OXO71 de tritilo en macacos Rhesus

Christopher D Kroenke1, Irene Canavesi2, Jenna N Castro3

  • 1Division of Neuroscience, Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, Oregon, USA.

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La obtención de imágenes de oxígeno por resonancia paramagnética electrónica (EPROI) con el radical tritilo OXO71 es segura en macacos Rhesus. Este estudio proporciona datos clave de farmacocinética y distribución tisular para optimizar la EPROI en humanos.

Palabras clave:
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Área de la Ciencia:

  • Imagen Biomédica
  • Física Médica
  • Farmacología

Sus antecedentes:

  • La obtención de imágenes de oxígeno por resonancia paramagnética electrónica (EPROI) cuantifica la presión parcial de oxígeno (pO2) in vivo.
  • OXO71 es un radical tritilo utilizado en EPROI, con aplicaciones previas en estudios en animales pequeños.
  • La traducción de EPROI al uso humano requiere optimización en modelos de animales grandes similares a los humanos.

Objetivo del estudio:

  • Caracterizar la farmacocinética de OXO71 después de la administración intravenosa en macacos Rhesus.
  • Determinar la distribución tisular de OXO71 en macacos Rhesus.
  • Evaluar la seguridad y viabilidad de OXO71 para EPROI en un modelo de primate.

Principales métodos:

  • Tres macacos Rhesus recibieron una inyección en bolo intravenoso de 92 μmol/kg de OXO71 durante 10 minutos.
  • Se recolectaron muestras de plasma y orina durante 2 horas después de la inyección.
  • Después de una segunda dosis, los animales fueron sacrificados y la distribución tisular se evaluó mediante imágenes de EPR.

Principales resultados:

  • La OXO71 en plasma exhibió una depuración bifásica con vidas medias inicial y terminal de 12,4 ± 1,2 min y 67,7 ± 8,9 min, respectivamente.
  • Se encontraron concentraciones apreciables de OXO71 en la mayoría de los tejidos, con la excepción del cerebro.
  • No se observaron efectos fisiológicos adversos, lo que indica baja toxicidad.

Conclusiones:

  • La EPROI utilizando OXO71 es segura y bien tolerada en primates.
  • Los datos de farmacocinética y distribución tisular informan sobre la dosis y el momento para la EPROI en animales grandes y humanos.
  • Estos hallazgos respaldan el desarrollo futuro de EPROI basada en OXO71 para aplicaciones clínicas.