Modification of the P-Glycoprotein Dependent Pharmacokinetics of Digoxin in Rats by Human Recombinant Interferon-α

Abstract

IFN-alpha induces in vivo a significant dose-dependent inhibitory effect on intestinal P-gp activity related to a local decrease in its expression, thereby predicting important clinical consequences when IFN-alpha and other P-gp substrates are associated.

Efavirenz Does Not Interact with the ABCB1 Transporter at the Blood—Brain Barrier

“…Therefore, the direct influence of EFV on P-gp function was examined at the BBB. Results showed that EFV did not alter the rat brain concentration of digoxin, a P-gp substrate (27). This was confirmed on GPNT cells, in which digoxin uptake remained unchanged with EFV.…”

Disposition of everolimus in mdr1a−/1b− mice and after a pre-treatment of lapatinib in Swiss mice

“…The concept of anatomical region-dependant modification of P-gp was already proposed to account for the inhibiting effect of some drugs on intestinal P-gp. For instance, IFN-α substantially inhibits P-glycoprotein expression in rats jejunum and ileum [26]. Quinidine increases ileal and jejunal digoxin absorption by inhibiting P-gp in rats [27].…”

Immunological Response as a Source to Variability in Drug Metabolism and Transport

“…Ben Reguiga et al (2005) have studies the effect of IFN-α on the pharmacokinetics of two different P-gp substrates in rats, namely digoxin and docetaxel. IFN-α given daily for 8 days to rats, was found to have a dose-dependent inhibitory effect on intestinal P-gp activity.…”