Abstracts

Levetiracetam (LEV) is a water-soluble antiepileptic drug and an IV preparation that has received an approval letter from the FDA at the time of the submission of this abstract. However, an IM formulation was not considered during development. The purpose of this pilot study was to obtain data regarding the safety and tolerability of the IV formulation administered intramuscularly to dogs., Animal experimentation approval was obtained and six dogs weighing approximately 20 kg were purchased. The same IV solution, intended for clinical use, was obtained from UCB Pharma. It contains 100 mg/ml LEV in an aqueous solution with a neutral pH. A standard animal discomfort rating scale was used. Dogs were injected with 5ml (500 mg) of LEV in one longissimus muscle, and 5 ml of saline in the contralateral muscle. Two dogs received IM LEV and control saline on Monday, two on Wednesday and two on Friday. This provided up to five days for reaction to develop. All were sacrificed on Saturday and 4 blocks of tissue of approximately 2 cm ³ were removed for standard histopathology. A standard four-point inflammation scale (0=no inflammation, 1=mild, 2=moderate, 4=marked) was used as well as examination for tissue damage., Tolerability: Three of the six dogs injected with LEV had slight head turning or a slight squirm; only one had slight vocalization, and 3 had no reaction. Three saline of six controls had slight head turning. Safety: The mean inflammation score for LEV was 0.28, and 0.62 for saline. One of the saline injected dogs had a score of 3 (moderate). Four dogs in each group had no inflammation., The IV preparation of LEV is well tolerated and safe when given as an IM injection to dogs. This suggests that the formulation may be useful in humans, but studies of safety and tolerability will need to be done., (Supported by UCB Pharma.)