title: Pharmacokinetics and blood-brain barrier transport of an anti-transferrin receptor monoclonal antibody (OX26) in rats after chronic treatment with the antibody.
abstract: Monoclonal antibodies (MAbs) directed against cell surface receptors (e.g. the transferrin receptor or the insulin receptor) on the brain capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo, are brain drug-delivery vectors. When cells are chronically exposed to MAbs in tissue culture, there is often down-regulation of the cell surface receptors. To examine whether similar down-regulation occurs in vivo, rats were chronically treated either with the OX26 murine MAb to the rat transferrin receptor or with a mouse IgG2a isotype control (0.25 mg/kg sc daily for 1 week), and the BBB transport of the OX26 MAb was then measured for both rat brain and liver in vivo. Although this treatment regimen resulted in a 41% increase in the permeability-surface area product for 125I-OX26 MAb transport into rat liver in vivo, there was no significant change in the BBB permeability-surface area product for the OX26 MAb. These studies indicate that repetitive administration of cell surface-specific MAbs does not necessarily result in down-regulation of BBB receptors.
authors.affiliation: Department of Medicine, University of California, Los Angeles, School of Medicine, USA.
authors.forename: D
authors.initials: D
authors.lastname: Wu
authors.forename: W M
authors.initials: WM
authors.lastname: Pardridge
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D011990:Receptors, Transferrin