Thesis
Biliary excretion of technetium-99m-sestamibi in wild-type dogs and in dogs with intrinsic (ABCB1-1[delta] mutation) extrinsic (ketoconazole treated) P-glycoprotein defiency
Master of Science (MS), Washington State University
2008
Handle:
https://hdl.handle.net/2376/101051
Abstract
P-glycoprotein (P-gp), the product of ABCB1 gene, is thought to contribute significantly to biliary excretion of a variety of drugs. Because a number of endogenous (ABCB1 polymorphisms) and exogenous (pharmacological P-gp inhibition) factors can interfere with normal P-gp function, efforts are being made to gain a better understanding of P-gp’s role in biliary drug excretion. The objective of this study was to compare biliary excretion of technetium-99m-sestamibi (99mTc-MIBI), a radio-labeled P-gp substrate, in wild-type dogs (ABCB1 wild/wild), P-gp deficient dogs (ABCB1 mut/mut), and dogs with presumed intermediate phenotype (ABCB1 mut/wild). The effect of pharmacological inhibition of P-gp (ketoconazole) on biliary excretion of 99mTc-MIBI in ABCB1 wild/wild dogs was also determined. Results of this study showed that ABCB1 mut/mut dogs have significant decreased biliary excretion of 99mTc-MIBI compared to ABCB1 wild/wild dogs. Biliary excretion of 99mTcMIBI in ABCB1 mut/wild dogs is not significantly different from ABCB1 wild/wild dogs. The P-gp inhibitor ketoconazole significantly decreased biliary excretion of 99mTc-MIBI. P-gp appears to play a major role in the biliary excretion of 99mTc-MIBI and likely other P-gp substrate drugs in dogs. This canine model may be useful for further studies delineating the role of P-gp in biliary drug excretion.
Metrics
5 File views/ downloads
12 Record Views
Details
- Title
- Biliary excretion of technetium-99m-sestamibi in wild-type dogs and in dogs with intrinsic (ABCB1-1[delta] mutation) extrinsic (ketoconazole treated) P-glycoprotein defiency
- Creators
- Joana Chaby Lara Santos Coelho
- Contributors
- Katrina L. Mealey (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Identifiers
- 99900525294101842
- Language
- English
- Resource Type
- Thesis