Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr 1a P-glycoprotein.

@article{Mayer1996SubstantialEO,
  title={Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr 1a P-glycoprotein.},
  author={Ulrich P. Mayer and E. B. Wagenaar and Jos H. Beijnen and Johan W. Smit and Dirk K. F. Meijer and J. van Asperen and Piet Borst and Alfred H Schinkel},
  journal={British journal of pharmacology},
  year={1996},
  volume={119 5},
  pages={1038-44}
}
1. We have used mice with a disrupted mdr 1a P-glycoprotein gene (mdr 1a (-/-) mice) to study the role of P-glycoprotein in the pharmacokinetics of digoxin, a model P-glycoprotein substrate. 2. [3H]-digoxin at a dose of 0.2 mg kg-1 was administered as a single i.v. or oral bolus injection. We focussed on intestinal mucosa and brain endothelial cells, two major pharmacological barriers, as the mdr 1a P-glycoprotein is the only P-glycoprotein normally present in these tissues. 3. Predominant… CONTINUE READING

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