Excessive Cyclosporine-Associated Immunosuppression in a Dog Heterozygous for the MDR1 (ABCB1-1Δ) Mutation

Abstract

Pharmacodynamic monitoring was used to titrate cyclosporine dosing in a dog with immune-mediated hemolytic anemia. Development of a suspected secondary infection, with subsequent discovery of an unexpectedly high level of T-cell suppression despite a relatively low cyclosporine dose, prompted an investigation into the cause of possible excessive immunosuppression. Blood cyclosporine concentrations were within expected target ranges, and the dog was determined to be heterozygous for the multidrug resistance protein 1 (MDR1; ATP-binding cassette sub family B member 1-1Δ) gene mutation. The MDR1 mutation was suspected to have contributed to the excessive immunosuppression experienced by this patient. This case highlights the need to monitor immunosuppressive therapy in the individual patient, especially when the patient is not responding to therapy at typical dosages or when secondary infections develop at dosages lower than expected to cause significant immunosuppression. Pharmacodynamic monitoring can be used to help identify unexpected excessive immunosuppression in dogs receiving cyclosporine, and MDR1 genotyping should be further explored as a potential method of predicting and preventing its occurrence.