Disposition of levetiracetam in healthy adult horses

Abstract

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 . 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.

Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals

“…administration to adult horses include yawning, low head carriage and drooling [14]. administration to adult horses include yawning, low head carriage and drooling [14].…”

“…A 5-7-day washout period was applied between each route of administration, which was calculated to be adequate even if the half-life in foals was twice that reported in adult horses [14]. or intragastrically (IG) using a randomised crossover design.…”

“…and orally and has been shown to be minimally sedating with few adverse effects in human patients [7]. Evaluation of the pharmacokinetics of levetiracetam in adult horses was recently performed [14] with a suggested target concentration of 35 mg/L, based on apparent therapeutic concentrations in other species. Although a therapeutic range has not been established in veterinary species, previous studies examining efficacy in cats, dogs and horses have utilised the therapeutic range established in human patients (5-45 mg/L).…”

“…Absorption is rapid and complete following oral administration with an excellent bioavailability of around 100% in all species that have been evaluated [11][12][13][14][15]. Although the pharmacokinetics of levetiracetam have been recently evaluated in the adult horse [14], dosages used in other species or recommended in adult horses cannot be directly extrapolated to foals due to critical differences in drug distribution and clearance in neonates [16][17][18][19]. Although the pharmacokinetics of levetiracetam have been recently evaluated in the adult horse [14], dosages used in other species or recommended in adult horses cannot be directly extrapolated to foals due to critical differences in drug distribution and clearance in neonates [16][17][18][19].…”

“…A target plasma concentration of 35 mg/l was used to establish dosing recommendations based on studies in adult horses [14]. and intragastric administration at a dose of 32 mg/kg bwt, and to establish a dosing interval which would maintain plasma levetiracetam concentrations within the proposed therapeutic range of 5-45 mg/L.…”