Canine and feline P-glycoprotein deficiency

In 2001, the molecular genetic basis of so-called "ivermectin sensitivity" in herding breed dogs was determined to be a P-glycoprotein deficiency caused by a genetic variant of the MDR1 (ABCB1) gene often called "the MDR1 mutation."  

Researchers have learned a great deal about P-glycoprotein's role in drug disposition since that discovery, namely that P-glycoprotein transports many more drugs than just macrocyclic lactones and that P-glycoprotein mediated drug transport is present in more places than just the blood brain barrier. Scientists have also discovered that some cats have a genetic variant of MDR1 that results in P-glycoprotein deficiency and that P-glycoprotein dysfunction can occur as a result of drug-drug interactions in any dog or cat. It has also been determined that the concept of P-glycoprotein "inhibitors" versus P-glycoprotein substrates is somewhat arbitrary and artificial.  

In this paper, researchers review these discoveries and discuss how they impact drug selection and dosing in dogs and cats with genetically mediated P-glycoprotein deficiency or P-glycoprotein dysfunction resulting from drug-drug interactions.  

The team concluded that a strategic, collaborative effort is needed to characterize the P-gp status of the hundreds of drugs used to treat canine and feline patients, preferably prior to a drug being marketed. In doing so, the authors said that serious and potentially fatal adverse drug reactions in dogs and cats can be prevented.

Katrina L Mealey, Jane Owens and Elaine Freeman. “Canine and feline P-glycoprotein deficiency: What we know and where we need to go.” J Vet Pharmacol Ther. 2022 Nov 3. doi: 10.1111/jvp.13102.

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