Intestinal absorption of miltefosine: contribution of passive paracellular transport.
Pharm Res
; 24(3): 546-54, 2007 Mar.
Article
en En
| MEDLINE
| ID: mdl-17252190
ABSTRACT
PURPOSE:
This study aimed to characterize the transepithelial transport of miltefosine (HePC), the first orally effective drug against visceral leishmaniasis, across the intestinal barrier to further understand its oral absorption mechanism. MATERIALS ANDMETHODS:
Caco-2 cell monolayers were used as an in vitro model of the human intestinal barrier. The roles of active and passive mechanisms in HePC intestinal transport were investigated and the relative contributions of the transcellular and paracellular routes were estimated.RESULTS:
HePC transport was observed to be pH-independent, partially temperature-dependent, linear as a function of time and non-saturable as a function of concentration. The magnitude of HePC transport was quite similar to that of the paracellular marker mannitol, and EDTA treatment led to an increase in HePC transport. Furthermore, HePC transport was found to be similar in the apical-to-basolateral and basolateral-to-apical directions, strongly suggesting that HePC exhibits non-polarized transport and that no MDR-mediated efflux was involved.CONCLUSIONS:
These results demonstrate that HePC crosses the intestinal epithelium by a non-specific passive pathway and provide evidence supporting a concentration-dependent paracellular transport mechanism, although some transcellular diffusion cannot be ruled out. Considering that HePC opens epithelial tight junctions, this study shows that HePC may promote its own permeation across the intestinal barrier.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosforilcolina
/
Absorción Intestinal
/
Modelos Biológicos
Límite:
Humans
Idioma:
En
Revista:
Pharm Res
Año:
2007
Tipo del documento:
Article
País de afiliación:
Francia