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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The complexity of intestinal absorption and exsorption of digoxin in rats.

The potential multiple carrier-mediated mechanisms involved in the transport of digoxin in rat intestine were investigated by the rapid filtration method in rat intestinal brush-border vesicles (BBMV) and in vitro Ussing chambers. The uptake of digoxin showed a typical overshoot phenomenon in the presence of an inward proton gradient and an outward bicarbonate gradient, or an outward glutathione gradient in BBMV. Good fitting to an equation consisting of both saturable and linear terms was obtained using non-linear regression analysis. GF120918, a specific P-gp inhibitor, significantly increased the absorptive permeability of digoxin in rat ileum (7.02x10(-7)cm/s versus 2.11x10(-6)cm/s with GF120918) but the addition of DIDS (0.5mM), an anionic transporter inhibitor, or bromosulfophthalein (0.1mM), an Oatp inhibitor, in the presence of GF120918 decreased the absorptive permeability compared with GF120918 alone (2.11x10(-6)cm/s versus 1.46x10(-6)cm/s, p<0.01 and 2.11x10(-6)cm/s versus 1.60x10(-6)cm/s, p<0.05, respectively). The above results suggest the involvement of carrier-mediated uptake mechanism, possibly Oatp, in digoxin absorption. Interestingly, GF120918 (1muM) did not abolish the polarized transport of digoxin in rat jejunum and ileum, and DIDS (0.5mM), not a P-gp inhibitor, and MK571 (50muM), an MRP-selective inhibitor, can also significantly decrease the exsorptive permeability of digoxin. This result indicates the involvement of non-P-gp efflux transporter in digoxin secretion and this transporter is DIDS and MK571-sensitive. Contrary to conventional concept, our studies show that intestinal absorption of digoxin may involve both active uptake and efflux transporters. Our study may have clinical implications in drug-drug or drug-food interactions involving transporters.[1]


  1. The complexity of intestinal absorption and exsorption of digoxin in rats. Yao, H.M., Chiou, W.L. International journal of pharmaceutics. (2006) [Pubmed]
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