Peer-reviewed veterinary case report
How ABCB1 gene affects heartworm prevention drugs in dogs
By Mealey, Katrina L·Published in Veterinary parasitology·2008·Department of Veterinary Clinical Sciences, United States·View original on PubMed →
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Original publication title: Canine ABCB1 and macrocyclic lactones: heartworm prevention and pharmacogenetics.
- Species:
- dog
Plain-English summary
A study found that certain herding breed dogs, like collies and Australian shepherds, can have a genetic mutation that makes them more sensitive to some medications, including heartworm preventatives. This mutation affects how their bodies process these drugs, but the good news is that all FDA-approved heartworm preventatives are safe to use at the recommended doses, even for dogs with this mutation. If you have a herding breed dog, it's still important to discuss their specific needs with your veterinarian, but you can feel confident using these heartworm medications as directed.
People also search for: collie heartworm prevention · Australian shepherd medication sensitivity · dog ABCB1 gene mutation
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 (ABCB1-1Delta) 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.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/18922637/