Pharmacokinetic and Pharmacodynamic Analysis of Loperamide in mdrla +/+ and -/- Mice

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dc.contributor.advisorPollack, Gary M.
dc.contributor.authorOlson, Emily R.
dc.descriptionvi, 20 p.en_US
dc.description.abstractThe division between the central and peripheral nervous system (CNS; PNS) is known as the blood brain barrier (BBB). One function of the BBB is to regulate transport between the central and peripheral compartments through a system of uptake and efflux transporters. An efflux transporter of particular interest is P-glycoprotein (P-gp) which serves to limit access of a variety of drugs, including HIV - protease inhibitors, chemotherapeutic compounds and various opioids, to the CNS. Following administration of the known P-gp substrates morphine and methadone to mice lacking P-gp, dramatic increases in opiate analgesia are observed as a result of increased brain penetration. This study utilizes another P-gp substrate known as loperamide, a member of the opioid family that fails to exhibit CNS effects despite its effectiveness in the PNS as an anti-diarrehal agent to assess differences in brain and serum concentrations and analgesia between P-gp deficient and competent mice. Following loperamide dosage, mice were tested for their ability to respond to painful stimuli in addition to collection of plasma and brain tissue. Assessment of pain response was judged using two sets of criteria, a standard criteria that judges for licking of the hind paws or jumping while the looser modified criteria also included withdrawal or shaking of the hind paw. The brain, serum and analgesia results were used to create a basic pharmacological assessment that demonstrates the increased NS penetration of loperamide in P-gp deficient mice. These results were used to describe differences in analgesia between the CNS and PNS as a consequence of the modified and standard criteria.en_US
dc.description.sponsorshipDrug Delivery and Disposition. School of Pharmacy. University of North Carolina. Chapel Hill, North Carolina.
dc.publisherKalamazoo Collegeen_US
dc.relation.ispartofKalamazoo College Biology Senior Individualized Projects Collection
dc.relation.ispartofseriesSenior Individualized Projects. Biology;
dc.rightsU.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.
dc.titlePharmacokinetic and Pharmacodynamic Analysis of Loperamide in mdrla +/+ and -/- Miceen_US