Clinical Applications of Therapeutic Drug Monitoring in Canine Idiopathic Epilepsy Patients Receiving Levetiracetam

Abstract

There are currently no drugs approved for the treatment of canine idiopathic epilepsy and as a result extra-label use of human-approved medications is common. Older agents such as phenobarbital are effective in dogs, but they are typically associated with severe side-effects or multiple drug-drug interactions. Newer agents, like levetiracetam (LEV) offer the potential for improved safety and efficacy when used for chronic therapy. Although the pharmacokinetic and pharmacodynamic profile of LEV in dogs has been studied in multiple trials, these trials have been small and most contained significant limitations. Thus, clinical equipoise remains regarding LEV efficacy, dosing, and the need for therapeutic drug monitoring (TDM). This retrospective study involving 205 dogs with idiopathic epilepsy was the largest retrospective analysis performed in a canine-population to-date. In this study, patient demographic data was summarized, AED use patterns were characterized, and logistic regression was used test the association between LEV concentrations in plasma and therapeutic response. The results suggest that LEV treatment success is more likely in patients who are treatment naïve and when LEV is initiated at a dose higher than is currently recommended. Upon conclusion of the study, there was no discernable correlation between LEV plasma drug concentration and therapeutic response; casting doubt on the overall need for therapeutic drug monitoring with LEV therapy. Despite this, evidence suggest that if used early and aggressively, LEV offers a reasonable alternative to traditional anti-epileptic therapy.