Levetiracetam Rectal Administration in Healthy Dogs

Abstract

BackgroundLevetiracetam is used to manage status epilepticus (SE) and cluster seizures (CS) in humans. The drug might be absorbed after rectal administration and could offer a practical adjunct to rectal administration of diazepam in managing SE and CS.HypothesisLevetiracetam is rapidly absorbed after rectal administration in dogs and maintains target serum concentrations for at least 9 hours.AnimalsSix healthy privately owned dogs between 2 and 6 years of age and weighing 10–20 kg.MethodsLevetiracetam (40 mg/kg) was administered rectally and blood samples were obtained immediately before (time zero) and at 10, 20, 40, 60, 90, 180, 360, and 540 minutes after drug administration. Dogs were observed for signs of adverse effects over a 24‐hour period after drug administration.Results C LEV at 10 minutes was 15.3 ± 5.5 μg/mL (mean, SD) with concentrations in the target range (5–40 μg/mL) for all dogs throughout the sampling period. C max (36.0 ± 10.7 μg/mL) and T max (103 ± 31 minutes) values were calculated and 2 disparate groups were appreciated. Dogs with feces in the rectum at the time of drug administration had lower mean C max values (26.7 ± 3.4 μg/mL) compared with those without (45.2 ± 4.4 μg/mL). Mild sedation was observed between 60 and 90 minutes without other adverse effects noted.Conclusions and Clinical ImportanceThis study supports the use of rectally administered levetiracetam in future studies of clinical effectiveness in the management of epileptic dogs.

Comparative single-dose pharmacokinetics of sildenafil after oral and rectal administration in healthy beagle dogs

“…We performed rectal administration of sildenafil ODF formulation, which is rapidly absorbed in the mucous membranes [ 12 ]. Some studies have reported rectal administration of medication as an alternative route for dogs that are not able to receive medication orally because of seizure [ 13 , 14 ]. However, previous studies demonstrated that the dosage for rectal administration should be adjusted because C max and AUC last (an indicator of bioavailability) after rectal dosing is relatively lower than that after oral administration.…”

Status epilepticus in dogs and cats, part 2: treatment, monitoring, and prognosis

“…In a small study of elderly people with nonconvulsive and convulsive SE, levetiracetam effectively terminated seizure activity when used as a first‐line treatment . Recently, target serum concentrations of levetiracetam were achieved after rectal administration in 6 healthy dogs, with the only adverse effect being mild and transient sedation …”

Intramuscular and rectal therapies of acute seizures

“…The C max was 36.0 ± 10.7 μg/mL and the T max 103 ± 31 min. Mild sedation was observed between 60 and 90 min, without other adverse effects noted [69].…”