Factors influencing serum concentrations of levetiracetam in dogs with epilepsy.

Abstract

BACKGROUND: Factors affecting serum concentrations of levetiracetam in dogs are unknown and could affect the efficacy of levetiracetam in controlling seizures in dogs with epilepsy. HYPOTHESIS/OBJECTIVES: Higher PO doses of levetiracetam will be needed in dogs to achieve serum concentrations shown to be effective in humans. Determine factors that could influence serum levetiracetam concentrations and justify dose adjustment in some epileptic dogs. ANIMALS: Sixty-nine client-owned dogs with epilepsy treated with levetiracetam alone or in combination, based on 127 trough serum concentration measurements of levetiracetam. METHODS: Retrospective cohort study. Linear mixed models were used to assess the effect of patient signalment and concurrent drug administration on serum concentrations of levetiracetam and the effect of serum concentration of levetiracetam on seizure frequency reduction. RESULTS: The PO dose of levetiracetam significantly explained changes in serum levetiracetam concentration, and this causal link was stronger with monotherapy (R&#x2009;=&#x2009;0.59, P&#x2009;<&#x2009;.001). Phenobarbital significantly decreased serum levetiracetam concentration in a dose dependent manner (R&#x2009;=&#x2009;0.30, P&#x2009;=&#x2009;.003). Based on our model, a levetiracetam dosage of 99-216&#x2009;mg/kg/day is necessary to obtain a serum levetiracetam concentration of 20&#x2009;&#x3bc;g/mL when used alone or concurrently with 7&#x2009;mg/kg/day of phenobarbital. No other factors were found to influence serum levetiracetam concentrations. No therapeutic range could be identified. CONCLUSION AND CLINICAL IMPORTANCE: Our data suggest that a dosage of 99-216&#x2009;mg/kg/day of levetiracetam is needed to achieve a serum concentration known to be therapeutically effective in humans, especially when administered concomitantly with phenobarbital.