EQUINE | Abstracts
Levetiracetam Pharmacokinetics
in Foals
Pharmacokinetics of the anticonvulsant levetiracetam in
neonatal foals
K. D. MacDonald, K. A. Hart,
J. L. Davis, L. J. Berghaus and
S. Giguère
Background Results
Objective Main limitations
Seizures are a common manifestation of neurological
disease in the neonatal foal and are an important cause
of morbidity and mortality in this population. Current
antiepileptic options are effective, but often have un-
desirable adverse effects, short duration of action and
high cost. Levetiracetam has an ideal safety and phar-
macokinetic profile in multiple species, including the
adult horse, and may be a safe and cost‐effective al-
ternative anticonvulsant in neonatal foals. Due to dif-
ferences in drug disposition and clearance dosages in
neonates, dosing recommendations in other species or
adult horses cannot be extrapolated to foals.
To establish the pharmacokinetic profile of single‐dose
i.v. and intragastric administration of levetiracetam in
healthy neonatal foals.
Study design
Randomised crossover experimental study.
Methods
Levetiracetam was administered as a single dose to six
healthy foals (ages 1–10 days) at a dose of 32 mg/kg
bwt i.v. or intragastrically. Plasma levetiracetam con-
centrations were measured using a validated HPLC
protocol.
18
After i.v. administration to healthy foals, levetirace-
tam had a mean (±s.d.) elimination half‐life of 7.76 ±
0.51 h, a mean systemic clearance of 61.67 ± 10.96
(mL/h/kg) and a mean apparent volume of distribu-
tion at steady state of 0.670 ± 0.124 (L/kg). Follow-
ing intragastric administration, levetiracetam had a
peak concentration of 38.34 ± 7.42 mg/L and time
to achieve peak concentration was 0.875 (0.5–1.5) h.
Mean bioavailability for IG administration was excel-
lent (103.04 ± 14.51%). No significant differences in
pharmacokinetic variables between routes and order
of administration were observed.
Small sample size and single‐dose administration.
Conclusions
Levetiracetam has excellent intragastric bioavailability
in foals and is predicted to maintain plasma concen-
trations at or above the proposed target concentration
with twice daily i.v. or oral administration. Once‐daily
administration may be possible in some foals based on
the therapeutic range recommended in other species.
http://onlinelibrary.wiley.com/doi/10.1111/evj.12790/full
• Equine Health Update •