CIVETAN   23983
CENTRO DE INVESTIGACION VETERINARIA DE TANDIL
Unidad Ejecutora - UE
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:
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