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Disposition of levetiracetam in healthy adult horses

Cesar, F. B., Stewart, A. J., Boothe, D. M., Ravis, W. R., Duran, S. H., Wooldridge, A. A.
Journal of veterinary pharmacology and therapeutics 2018 v.41 no.1 pp. 92-97
adults, bioavailability, blood serum, cross-over studies, enteral feeding, half life, horses, humans, immunoassays, intravenous injection, pharmacodynamics
Nine horses received 20 mg/kg of intravenous (LEVIV); 30 mg/kg of intragastric, crushed immediate release (LEVCIR); and 30 mg/kg of intragastric, crushed extended release (LEVCER) levetiracetam, in a three‐way randomized crossover design. Crushed tablets were dissolved in water and administered by nasogastric tube. Serum samples were collected over 48 hr, and levetiracetam concentrations were determined by immunoassay. Mean ± SD peak concentrations for LEVCIR and LEVCER were 50.72 ± 10.60 and 53.58 ± 15.94 μg/ml, respectively. The y‐intercept for IV administration was 64.54 ± 24.99 μg/ml. The terminal half‐life was 6.38 ± 1.97, 7.07 ± 1.93 and 6.22 ± 1.35 hr for LEVCIR, LEVCER, and LEVIV, respectively. Volume of distribution at steady‐state was 630 ± 73.4 ml/kg. Total body clearance after IV administration was 74.40 ± 19.20 ml kg⁻¹ hr⁻¹. Bioavailability was 96 ± 10, and 98 ± 13% for LEVCIR and LEVCER, respectively. A single dose of Levetiracetam (LEV) was well tolerated. Based on this study, a recommended dosing regimen of intravenous or oral LEV of 32 mg/kg every 12 hr is likely to achieve and maintain plasma concentrations within the therapeutic range suggested for humans, with optimal kinetics throughout the dosing interval in healthy adult horses. Repeated dosing and pharmacodynamic studies are warranted.