Journal article
Canine ABCB1 and macrocyclic lactones: Heartworm prevention and pharmacogenetics
Veterinary parasitology, Vol.158(3), pp.215-222
2008
Handle:
https://hdl.handle.net/2376/101617
PMID: 18922637
Abstract
The impact of drug transporters on drug pharmacokinetics and pharmacodynamics has been increasingly recognized in recent years. P-glycoprotein (P-gp), the product of the
ABCB1 (formerly
MDR1) gene, is among the most well-characterized drug transporters, particularly in veterinary medicine. P-gp is expressed by a variety of normal tissues, including the intestines, brain capillary endothelial cells, renal tubular cells, and biliary canalicular cells, 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 and enhances their excretion from the body. Many drugs used in veterinary medicine are substrates for P-gp, including many chemotherapeutic agents and macrocyclic lactones (avermectins and milbemycin). A 4-base pair deletion mutation in the
ABCB1 gene occurs in many herding breed dogs, including collies, Australian shepherds, and Shetland sheepdogs. The mutation (
ABCB1-
1Δ) renders affected animals extremely susceptible to toxicosis induced by substrate drugs, such as the macrocyclic lactones at doses well below those tolerated by dogs with the wild-type
ABCB1 gene. However, at the manufacturer’s recommended dose, all FDA-approved heartworm preventive products marketed in the United States are safe, even for dogs with the
ABCB1 mutant/mutant genotype.
Metrics
9 Record Views
Details
- Title
- Canine ABCB1 and macrocyclic lactones: Heartworm prevention and pharmacogenetics
- Creators
- Katrina L Mealey - Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-6610, United States
- Publication Details
- Veterinary parasitology, Vol.158(3), pp.215-222
- Academic Unit
- Veterinary Clinical Sciences, Department of
- Publisher
- Elsevier B.V
- Identifiers
- 99900546687101842
- Language
- English
- Resource Type
- Journal article