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Related Experiment Videos

Ivermectin excretion by isolated functionally intact brain endothelial capillaries.

S Nobmann1, B Bauer, G Fricker

  • 1Institute of Pharmaceutical Technology and Biopharmacy, University of Heidelberg, D-69120 Heidelberg, Germany.

British Journal of Pharmacology
|February 13, 2001
PubMed
Summary

This study demonstrates that Ivermectin is transported across the blood-brain barrier via p-glycoprotein (Pgp) in brain capillaries. This finding reveals a cellular mechanism for Ivermectin

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • The blood-brain barrier (BBB) tightly regulates the passage of substances into the brain.
  • p-glycoprotein (Pgp) is a key efflux transporter located at the BBB, influencing drug disposition.
  • Understanding drug transport mechanisms at the BBB is crucial for effective neurological therapies.

Purpose of the Study:

  • To investigate the interaction of Ivermectin with p-glycoprotein (Pgp) at the porcine blood-brain barrier.
  • To elucidate the cellular mechanisms of Ivermectin transport across brain endothelial capillaries.
  • To determine if Ivermectin is a substrate or inhibitor of Pgp.

Main Methods:

  • Isolation of functionally intact porcine brain endothelial capillaries.

Related Experiment Videos

  • Immunohistochemistry and Western blot to localize and confirm p-glycoprotein expression.
  • Confocal laser scanning microscopy to visualize and quantify BODIPY-Ivermectin accumulation in capillaries.
  • Inhibition studies using specific Pgp inhibitors (PSC-833, Cyclosporin A, Verapamil) and substrates.

    • Main Results:

    • p-Glycoprotein was localized to the lumenal membrane of isolated brain capillaries.
    • BODIPY-Ivermectin secretion into the capillary lumen showed characteristics of specific, energy-dependent transport.
    • Ivermectin and Pgp inhibitors (PSC-833, Cyclosporin A, Verapamil) significantly affected lumenal BODIPY-Ivermectin levels.
    • Ivermectin inhibited the Pgp-mediated secretion of BODIPY-Verapamil, and vice versa.
    • No interaction was observed with multidrug resistance-related protein (MRP) transporters.

    Conclusions:

    • Ivermectin is transported across the lumenal membrane of brain capillaries, likely mediated by p-glycoprotein.
    • This study provides the first cellular-level evidence of Ivermectin's Pgp interaction at the blood-brain barrier.
    • The findings have implications for understanding Ivermectin's brain penetration and potential drug-drug interactions.