Journal article
Therapeutic implications of the MDR-1 gene
Journal of veterinary pharmacology and therapeutics, Vol.27(5), pp.257-264
10/2004
Handle:
https://hdl.handle.net/2376/104249
PMID: 15500562
Abstract
Drug transporters significantly influence drug pharmacokinetics and pharmacodynamics. P-glycoprotein (P-gp), the product of the MDR1 (ABCB1) gene, is among the most well-characterized drug transporters, particularly in veterinary medicine. A number of clinically relevant, structurally and functionally unrelated drugs are substrates for P-gp. P-gp is expressed by a variety of normal tissues including the intestines, renal tubular cells, brain capillary endothelial cells, biliary canalicular cells, and others, where it functions to actively extrude substrate drugs. In this capacity, P-gp limits oral absorption and central nervous system entry of many substrate drugs. A number of MDR1 polymorphisms have been described in human patients, some of which result in altered drug pharmacokinetics and susceptibility to diseases such as Parkinson's disease, inflammatory bowel disease, refractory seizures, and others. An MDR1 polymorphism in herding breed dogs, including collies and Australian shepherds, has been demonstrated to be the cause of ivermectin sensitivity in these breeds. Recent evidence suggests that this polymorphism, a 4-bp deletion mutation, results in increased susceptibility to the toxicity of several drugs in addition to ivermectin. Furthermore, data in rodent models suggest that P-gp may play an important role in regulating the hypothalamic-pituitary-adrenal axis.
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Details
- Title
- Therapeutic implications of the MDR-1 gene
- Creators
- K L Mealey - Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610, USA. kmealey@vetmed.wsu.edu
- Publication Details
- Journal of veterinary pharmacology and therapeutics, Vol.27(5), pp.257-264
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- England
- Identifiers
- 99900546642201842
- Language
- English
- Resource Type
- Journal article