The effect of protein binding on ivermectin uptake by bovine brain microvessel endothelial cells.
The effect of albumin binding on ivermectin uptake and transfer across the endothelial component of the blood-brain barrier (BBB) was determined with an in vitro model comprised of bovine brain microvessel endothelial cell (BMEC) monolayers. Cellular uptake of ivermectin was limited in the absence of albumin and 90% inhibited in the presence of 10% albumin. Cell membrane association of ivermectin, as followed by fluorescent probe labelling, was observed only at high (micromolar) concentrations of the drug. Membrane association was about 75% inhibited in the presence of albumin. Similarly, transfer across BMEC monolayers was restricted, equivalent to that of BBB impermeant markers. Unlike the uptake studies, however, albumin had little effect on the transfer of ivermectin across BMEC monolayers. These results support recent in vivo findings on the distribution of ivermectin into the brain and suggest that ivermectin has only a limited affinity for the endothelial component of the normal BBB.
Audus
K L
KL
Department of Pharmaceutical Chemistry, University of Kansas, School of Pharmacy, Lawrence 66045.
Knaub
S R
SR
Guillot
F L
FL
Schaeffer
J M
JM
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002417:Cattle / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005454:Fluorescence Polarization; D007559:Ivermectin / Q000493:pharmacokinetics*; D008833:Microcirculation / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology
D007559:Ivermectin