Pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals

Abstract

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.

Levetiracetam pharmacokinetics and its covariates: proposal for optimal dosing in the paediatric population

“…In our study, the average Vd and CL values were within the range reported in other studies; however, there are only a few original studies of levetiracetam pharmacokinetics in the paediatric population 10 13–18…”

Highlights of recent clinically relevant papers

“…In this randomised crossover study Katherine MacDonald and colleagues in the USA aimed to describe the pharmacokinetics of the anticonvulsant levetiracetam in neonatal foals .…”

Clinical insights: Recent development in equine neonatology and foal medicine (2017–2019)

“…To date, seizures have been successfully treated primarily with diazepam or midazolam in emergency situations and phenobarbital for long‐term control . Although efficacious, these medications have undesirable and potentially dangerous side effects such as sedation, respiratory depression and toxicity . Other anti‐epileptic drugs such as gabapentin and pregabalin have been evaluated in horses, but their use is limited by poor bioavailability along with the side effects of sedation and colic .…”

“…Other anti‐epileptic drugs such as gabapentin and pregabalin have been evaluated in horses, but their use is limited by poor bioavailability along with the side effects of sedation and colic . A recent publication described the use of the novel anti‐epileptic drug levetiracetam in healthy neonatal foals which may provide improved seizure control while having more favourable safety and tolerability over other medications . The exact mechanism of action of levetiracetam is still being elucidated, but the drug likely gains its benefits by binding to and reducing the rate of vesicle release of synaptic vesicle protein SV2A, which is a synaptic vesicle membrane protein expressed in neurons and endocrine cells and is involved in the regulation of neurotransmitter release .…”

“…The exact mechanism of action of levetiracetam is still being elucidated, but the drug likely gains its benefits by binding to and reducing the rate of vesicle release of synaptic vesicle protein SV2A, which is a synaptic vesicle membrane protein expressed in neurons and endocrine cells and is involved in the regulation of neurotransmitter release . This medication has been shown to be safe and efficacious in people, dogs and cats, has minimal protein binding, few drug‐drug interactions and can be administered either intravenously or orally with reportedly minimal side effects ; it has also been reported to be well tolerated in healthy adult horses . In the pharmacokinetic study, dosing models predicted that twice‐daily administration of 32 mg/kg either orally or intravenously would maintain plasma concentrations within the proposed target concentration throughout the dosing interval.…”