Levetiracetam is a pyrrolidone-derived anticonvulsant used in both human and veterinary medicine for the management of epilepsy. Owing to its central nervous system effects, including mood-stabilising and anxiolytic properties, levetiracetam has been classified as a potential performance-modifying agent in competitive animals. This study aimed to characterise the plasma elimination and urinary excretion profiles of levetiracetam and its primary metabolite, levetiracetam carboxylic acid, following oral administration in greyhounds.
Six greyhounds were administered a single oral dose of levetiracetam (20 mg/kg) in the form of Keppra® tablets. Plasma and urine samples were collected over a 120 hour period and analysed using a validated dilute-and-shoot liquid chromatography-tandem mass spectrometry (LC-MS/MS) method on a Shimadzu 8050 instrument employing multiple reaction monitoring (MRM). The method validation demonstrated acceptable sensitivity, linearity, accuracy, and precision for levetiracetam in both matrices. Due to matrix effects, levetiracetam carboxylic acid concentrations were estimated rather than accurately quantified.
Appropriate pharmacokinetic analysis was performed. In plasma, levetiracetam reached peak concentrations (Cmax) between 0.5 and 2 hours post-administration and was quantifiable up to 24 hours. Levetiracetam carboxylic acid was observed between 2 and 10 hours, and detectable up to 24 hours.
In urine, levetiracetam reached Cmax between 4 and 8 hours post-administration, with detection up to 72 hours. Levetiracetam carboxylic acid reached estimated Cmax between 4 and 10 h and detectable in some dogs up to 72 hours.
These results demonstrate the rapid absorption and elimination of levetiracetam in greyhounds and the substantial urinary excretion of both the parent drug and its metabolite. Monitoring of both levetiracetam and levetiracetam carboxylic acid in routine doping control urine samples can control the misuse of levetiracetam in greyhounds.