pgp - publications

Predict more pgp - ligand interactions now!

1. J Vet Pharmacol Ther. 2012 Mar 19. doi: 10.1111/j.1365-2885.2012.01390.x. [Epub
ahead of print]

The effect of P-Glycoprotein on methadone hydrochloride flux in equine intestinal

Linardi RL, Stokes AM, Andrews FM.

Equine Health Studies Program (EHSP), Department of Veterinary Clinical Sciences,
School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA, USA
Department of Human Nutrition, Food and Animal Sciences, College of Tropical
Agriculture and Human Resources, University of Hawaii, Honolulu, HI, USA.

Linardi, R. L., Stokes, A. M., Andrews, F. M. The effect of P-Glycoprotein on
methadone hydrochloride flux in equine intestinal mucosa. J. vet. Pharmacol.
Therap. doi: 10.1111/j.1365-2885.2012.01390.x. Methadone is an effective
analgesic opioid that may have a place for the treatment of pain in horses.
However, its absorption seems to be impaired by the presence of a transmembrane
protein, P-glycoprotein, present in different tissues including the small
intestine in other species. This study aims to determine the effect of the
P-glycoprotein on methadone flux in the equine intestinal mucosa, as an indicator
of in vivo drug absorption. Jejunum tissues from five horses were placed into the
Ussing chambers and exposed to methadone solution in the presence or absence of
Rhodamine 123 or verapamil. Electrical measurements demonstrated tissue viability
for 120 min, and the flux of methadone across the jejunal membrane (mucosal to
submucosal direction) was calculated based on the relative drug concentration
measured by ELISA. The flux of methadone was significantly higher only in the
presence of verapamil. P-glycoprotein was immunolocalized in the apical membrane
of the jejunal epithelial cells (enterocytes), mainly located in the tip of the
villi compared to cells of the crypts. P-glycoprotein is present in the equine
jejunum and may possibly mediate the intestinal transport of methadone. This
study suggests that P-glycoprotein may play a role in the poor intestinal
absorption of methadone in vivo.

© 2012 Blackwell Publishing Ltd.

PMID: 22428876 [PubMed - as supplied by publisher]