All Breeds
Canine Multidrug Sensitivity (MDR1) is an inherited pharmacogenetic disorder caused by a mutation in the multidrug resistance gene (MDR1, also known as ABCB1). This gene encodes P-glycoprotein, a critical transmembrane efflux pump involved in limiting drug penetration into the brain and facilitating drug elimination through the blood–brain barrier, intestinal epithelium, liver, and kidneys.
Dogs carrying the MDR1 mutation have reduced or absent functional P-glycoprotein. As a result, certain drugs are not efficiently transported out of the brain or eliminated from the body, leading to excessive central nervous system exposure and increased systemic drug concentrations. This altered pharmacokinetic profile significantly increases the risk of adverse drug reactions.
Although the mutation can occur in any breed, increased prevalence has been documented in Collies, Australian Shepherds, Longhaired Whippets, and related herding breeds. However, because mixed-breed dogs may also carry the mutation, breed alone is not a reliable predictor of risk.
Clinically, affected dogs may develop neurologic toxicity following administration of P-glycoprotein substrate drugs. Reported signs include hypersalivation, ataxia, tremors, blindness, depression, disorientation, coma, respiratory compromise, and death. Severity depends on drug type, dose, and the dog’s genetic status. Dogs heterozygous for the mutation may exhibit milder or dose-dependent adverse effects.
Drugs documented or strongly suspected to cause adverse reactions in MDR1-affected dogs include, but are not limited to:
Acepromazine, Butorphanol, Cyclosporine, Digoxin, Doxorubicin, Ivermectin, Loperamide, Moxidectin, Vinblastine, and Vincristine.
Biochemical studies indicate that P-glycoprotein interacts with more than 50 drugs, and additional agents such as Domperidone, Etoposide, Mitoxantrone, Morphine, Ondansetron, Paclitaxel, Quinidine, and Rifampicin may also pose risk.
The DNA-based MDR1 test directly detects the causative mutation in the ABCB1 gene, allowing definitive classification of dogs as genetically normal, heterozygous (carrier), or affected (homozygous mutant). Because the causative mutation is directly analyzed, diagnostic accuracy is considered 100%.
From a clinical standpoint, this test is a critical tool for safe drug selection and dosing, particularly prior to administration of antiparasitic, chemotherapeutic, anesthetic, or neurologically active medications. Rather than empirically avoiding certain drugs in predisposed breeds, veterinarians can use genetic results to guide individualized treatment decisions, reduce adverse drug events, and improve patient safety.