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Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals
Author(s) -
MacDonald K. D.,
Hart K. A.,
Davis J. L.,
Berghaus L. J.,
Giguère S.
Publication year - 2018
Publication title -
equine veterinary journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.82
H-Index - 87
eISSN - 2042-3306
pISSN - 0425-1644
DOI - 10.1111/evj.12790
Subject(s) - levetiracetam , pharmacokinetics , medicine , volume of distribution , dosing , anticonvulsant , pharmacology , dose , bioavailability , adverse effect , population , crossover study , phenytoin , foal , anesthesia , epilepsy , biology , alternative medicine , environmental health , pathology , psychiatry , genetics , placebo
Summary Background 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 undesirable adverse effects, short duration of action and high cost. Levetiracetam has an ideal safety and pharmacokinetic profile in multiple species, including the adult horse, and may be a safe and cost‐effective alternative anticonvulsant in neonatal foals. Due to differences in drug disposition and clearance dosages in neonates, dosing recommendations in other species or adult horses cannot be extrapolated to foals. Objective 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 concentrations were measured using a validated HPLC protocol. Results After i.v. administration to healthy foals, levetiracetam 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 distribution at steady state of 0.670 ± 0.124 (L/kg). Following 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 excellent (103.04 ± 14.51%). No significant differences in pharmacokinetic variables between routes and order of administration were observed. Main limitations Small sample size and single‐dose administration. Conclusions Levetiracetam has excellent intragastric bioavailability in foals and is predicted to maintain plasma concentrations 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.