INVESTIGADORES
VIRKEL Guillermo Leon
artículos
Título:
Intestinal drug transport: Ex vivo evaluation of the interactions between ABC transporters and anthelmintic molecules
Autor/es:
BALLENT, M., MATÉ, L., VIRKEL, G., SALLOVITZ, J., VIVIANI, P., LANUSSE, C., LIFSCHITZ, A.
Revista:
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Lugar: Londres; Año: 2014 vol. 37 p. 332 - 337
ISSN:
0140-7783
Resumen:
The family of ATP-binding cassette (ABC) transporters is composed of
several transmembrane proteins that are involved in the efflux of a
large number of drugs including ivermectin, a macrocyclic lactone (ML)
endectocide, widely used in human and livestock antiparasitic therapy.
The aim of the work reported here was to assess the interaction between
three different anthelmintic drugs with substrates of the P-glycoprotein
(P-gp) and the breast cancer resistance protein (BCRP). The ability of
ivermectin (IVM), moxidectin (MOX) and closantel (CST) to modulate the
intestinal transport of both rhodamine 123 (Rho 123), a P-gp substrate,
and danofloxacin (DFX), a BCRP substrate, across rat ileum was studied
by performing the Ussing chamber technique. Compared to the controls,
Rho 123 efflux was significantly reduced by IVM (69%), CST (51%) and the
positive control PSC833 (65%), whereas no significant differences were
observed in the presence of MOX (30%). In addition, DFX efflux was
reduced between 59% and 72% by all the assayed drug molecules, showing a
higher potency than that observed in the presence of the specific BCRP
inhibitor pantoprazole (PTZ) (52%). An ex vivo intestinal transport
approach based on the diffusion chambers technique may offer a
complementary tool to study potential drug interactions with efflux
transporters such as P-gp and BCRP.