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Disposition of levetiracetam in healthy adult horses
Author(s) -
Cesar F. B.,
Stewart A. J.,
Boothe D. M.,
Ravis W. R.,
Duran S. H.,
Wooldridge A. A.
Publication year - 2018
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12417
Subject(s) - levetiracetam , dosing , crossover study , bioavailability , pharmacokinetics , medicine , volume of distribution , pharmacology , pharmacodynamics , anesthesia , alternative medicine , pathology , psychiatry , epilepsy , placebo
Nine horses received 20 mg/kg of intravenous ( LEV IV ); 30 mg/kg of intragastric, crushed immediate release ( LEV CIR ); and 30 mg/kg of intragastric, crushed extended release ( LEV CER ) 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 LEV CIR and LEV CER 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 LEV CIR , LEV CER , and LEV IV , 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 LEV CIR and LEV CER , 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.