|dc.contributor.advisor||Pollack, Gary M.||
|dc.contributor.author||Olson, Emily R.||
|dc.description||1 broadside : ill.||
|dc.description.abstract||P-glycoprotein (P-gp), is a transmembrane protein located in the bloodbrain
barrier (BBB) that limits access of a variety of drugs, including HIVprotease
inhibitors, immunosuppresants chemotherapeutic compounds
and opioids, to the CNS.
P-gp is thought to play a protective role by excluding substrates from entry
into the bloodstream and by facilitation substrate elimination from the body
and from penetrating into a variety of “sanctuary” tissue spaces
representing organs that are prone to toxic insult such as the brain.
Loperamide (Immodium-AD) is a unique member of the opioid family
because it exhibits pronounced peripheral affects while remaining relatively
impermeable at the BBB and therefore ineffective in the CNS.
Previous work with morphine, methadone and loperamide in P-gp
competent [mdr1a (+/+)] and deficient [mdr1a (-/-)] mice have
demonstrated that mice lacking P-gp exhibit enhanced brain
concentrations and analgesic effects.
A comprehensive in vivo description of the ability of P-gp to modulate
analgesia, and in particular the degree to which changes in analgesia
correlate with altered distribution of loperamide within the body, is lacking.
The primary objective of the present study was to assess the role of P-gp
in the pharmacokinetics (PK; drug concentrations over time) and
pharmacodynamics (PD; ability to minimize apparent discomfort in the
presence of painful stimuli) of loperamide.||en
|dc.description.sponsorship||Kalamazoo College. Department of Biology. Diebold Symposium, 2004||
|dc.description.sponsorship||University of North Carolina at Chapel Hill.||
|dc.description.tableofcontents||Introduction -- Methods -- Results -- Conclusions -- Future directions -- Acknowledgments||
|dc.title||Pharmacokinetics and Pharmacodynamics of Loperamide in mdr1a (+/+) and mdr1a (-/-) Mice||en