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Biliary excretion of technetium-99m-sestamibi in wild-type dogs and in dogs with intrinsic (ABCB1-1Δ mutation) and extrinsic (ketoconazole treated) P-glycoprotein deficiency
- Source :
- Journal of Veterinary Pharmacology and Therapeutics. 32:417-421
- Publication Year :
- 2009
- Publisher :
- Wiley, 2009.
-
Abstract
- P-glycoprotein (P-gp), the product of ABCB1 gene, is thought to play a role in the biliary excretion of a variety of drugs, but specific studies in dogs have not been performed. Because a number of endogenous (ABCB1 polymorphisms) and exogenous (pharmacological P-gp inhibition) factors can interfere with normal P-gp function, a better understanding of P-gp's role in biliary drug excretion is crucial in preventing adverse drug reactions and drug-drug interactions in dogs. The objectives of this study were to compare biliary excretion of technetium-99m-sestamibi ((99m)Tc-MIBI), a radio-labelled P-gp substrate, in wild-type dogs (ABCB1 wild/wild), and dogs with intrinsic and extrinsic deficiencies in P-gp function. Dogs with intrinsic P-gp deficiency included ABCB1 mut/mut dogs, and dogs with presumed intermediate P-gp phenotype (ABCB1 mut/wild). Dogs with extrinsic P-gp deficiency were considered to be ABCB1 wild/wild dogs treated with the P-gp inhibitor ketoconazole (5 mg/kg PO q12h x 9 doses). Results from this study indicate that ABCB1 mut/mut dogs have significantly decreased biliary excretion of (99m)Tc-MIBI compared with ABCB1 wild/wild dogs. Treatment with ketoconazole significantly decreased biliary excretion of (99m)Tc-MIBI in ABCB1 wild/wild dogs. P-gp appears to play an important role in the biliary excretion of (99m)Tc-MIBI in dogs. It is likely that concurrent administration of a P-gp inhibitor such as ketoconazole will decrease P-gp-mediated biliary excretion of other substrate drugs as well.
- Subjects :
- Male
Technetium Tc 99m Sestamibi
medicine.medical_specialty
ATP-binding cassette transporter
Endogeny
Pharmacology
Excretion
Dogs
Polymorphism (computer science)
Internal medicine
medicine
Animals
Bile
Drug Interactions
Gamma Cameras
ATP Binding Cassette Transporter, Subfamily B, Member 1
Adverse effect
P-glycoprotein
Polymorphism, Genetic
General Veterinary
biology
Wild type
Gallbladder
Ketoconazole
Endocrinology
biology.protein
Female
medicine.drug
Subjects
Details
- ISSN :
- 13652885 and 01407783
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Journal of Veterinary Pharmacology and Therapeutics
- Accession number :
- edsair.doi.dedup.....9ae0e5e56a4d0a66245030fd5d49e347
- Full Text :
- https://doi.org/10.1111/j.1365-2885.2009.01068.x