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Intramuscular, intravenous and oral levetiracetam in dogs: safety and pharmacokinetics
Authors:Patterson E E  Goel V  Cloyd J C  O'Brien T D  Fisher J E  Dunn A W  Leppik I E
Institution:Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN, USA;;Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN, USA;;Veterinary Population Medicine, University of Minnesota, St. Paul, MN, USA;;MINCEP Epilepsy Care, Minneapolis, MN, USA;;Department of Neurology, University of Minnesota, Minneapolis, MN, USA
Abstract:Intravenous (IV) levetiracetam (LEV) is available for humans for bridge therapy when the oral route is unavailable. We investigated the safety and pharmacokinetics of LEV administered intramuscularly (IM), IV, and orally to dogs.
Six Hound dogs received 19.5–22.6 mg/kg of LEV IM, IV and orally with a wash-out period in between. All dogs received 500 mg LEV orally and 5 mL of 100 mg/mL LEV IM. Three dogs received 500 mg of LEV IV and three dogs received 250 mg LEV IV with 250 mg given perivascularly to approximate extravasation. Safety was assessed using a pain scale at time of IM administration and histopathological examination 24 h to 5 days after injection.
Intravenous LEV half-life was 180 ± 18 min. Bioavailability of IM LEV was 100%. Mean time to Tmax after IM was 40 ± 16 min. The mean Cmax IM was 30.3 ± 3 μg/mL compared to the C0 of 37 ± 5 μg/mL for IV. Mean inflammation score (0–4 scale) for IM LEV was 0.28 and for saline 0.62. Extravasation did not cause tissue damage.
Parenteral LEV is well tolerated and appears safe following IM and IV injections in dogs. Parenteral LEV should be evaluated for use in dogs with epilepsy.
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