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In Vivo Evaluation of the Role of P-glycoprotein on the Transport of DAMGO over Blood-Brain Barrier
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
2012 (English)Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

The purpose of this study is to evaluate the role of P-glycoprotein on the transport of DAMGO across the blood-brain barrier in vivo. Two groups of Sprague-Dawley rats (n=6) received 60 µg/kg/min DAMGO for 300 minutes as a constant iv. infusion. After 120 minutes the two groups received an iv. infusion of either 30 mg/kg cyclosporine or 10 mg/kg elacridar as  P-glycoprotein (P-gp) inhibitors. The unbound DAMGO concentrations in brain and blood were monitored using microdialysis. 10 µl microdialysis samples were collected every 20 minutes. Blood samples were collected according to schedule to measure plasma concentrations of elacridar and blood concentrations of cyclosporine. The concentration-time curve of DAMGO following 30 mg/kg cyclosporine infusion showed a 2.5-3 fold increase in both brain and blood concentrations of DAMGO. This synchronized increase keeps unbound brain-blood concentration ratio (Kp, uu) almost unchanged (0.04 before CyA infusion and 0.06 after). Elacridar which is a more specific inhibitor for P-gp had no effect on neither blood nor brain DAMGO concentrations.

In conclusion, the effect of cyclosporine could be explained by it altering DAMGO´s plasma pharmacokinetics and the ineffectiveness of Elacridar on the Kp,uu makes relating DAMGO to P-gp inconclusive. 

Place, publisher, year, edition, pages
2012. , 24 p.
Keyword [en]
Microdialysis, DAMGO, BBB, Kpuu, Cyclosporine, Elacridar.
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:uu:diva-185045OAI: oai:DiVA.org:uu-185045DiVA: diva2:570414
Subject / course
Pharmacokinetics
Educational program
Master of Science Programme in Pharmacy
Presentation
2012-05-30, BMC, Uppsala, 10:20 (Swedish)
Uppsok
Medicine
Supervisors
Examiners
Available from: 2012-11-19 Created: 2012-11-19 Last updated: 2012-11-19Bibliographically approved

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