RESUMEN
It has been shown that vasoconstrictive drugs such as ephedrine derivatives are able to decrease systemic absorption of drugs administered by mucosal surfaces. The present paper set out to evaluate in the rat model the effect of co-administered nasal ephedrine on the absorption of GR138950 in a simple and in a pectin self-gelling formulation. It was hypothetised that a decrease in nasal systemic absorption would lead to an increase in direct nose-to-brain transport as demonstrated by the drug concentration in the olfactory lobes of the brain. It was found that ephedrine administered nasally with the drug in a simple aqueous solution resulted in a significant increase in nasal systemic absorption and also an increase in brain delivery; however, this trend was not observed with the pectin formulations. The pectin formulation with ephedrine resulted in lower systemic absorption of GR138950 and lower brain uptake compared to the simple solution formulation containing ephedrine.
Asunto(s)
Benzofuranos/farmacocinética , Sistema Nervioso Central/metabolismo , Efedrina/farmacología , Cavidad Nasal/metabolismo , Administración Intranasal , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Bloqueadores del Receptor Tipo 1 de Angiotensina II/química , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacocinética , Animales , Área Bajo la Curva , Benzofuranos/sangre , Benzofuranos/química , Disponibilidad Biológica , Transporte Biológico/efectos de los fármacos , Evaluación Preclínica de Medicamentos/métodos , Efedrina/administración & dosificación , Geles , Masculino , Estructura Molecular , Bulbo Olfatorio/metabolismo , Pectinas/química , Ratas , Ratas Wistar , Soluciones , Factores de Tiempo , Distribución Tisular/efectos de los fármacos , Vasoconstrictores/administración & dosificación , Vasoconstrictores/farmacología , AguaRESUMEN
Absorption windows in the proximal gut can limit the bioavailability of orally administered compounds and can be a major obstacle to the development of controlled release formulations for important drugs. Methods to increase the residence of drug formulations at or above the absorption window are discussed in this review. Two main approaches are presently being explored: (i) bioadhesive microspheres that have a slow intestinal transit; and (ii) the gastroretentive dosage system, which is based on multiparticulates or large single unit systems. A good understanding of gastrointestinal transit in humans and the effect of factors such as food can be helpful in the design of rational systems that will have clinical benefit.