Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats

Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats

Smith C, Barnes Heller HL, Reif N, Van Hesteren M, Reinhart JM. Serum levetiracetam concentrations after transdermal levetiracetam administration, 3 times daily, to healthy cats. J Vet Intern Med. 2019;1–4.

Seizures in cats may be treated with a variety of medications. While phenobarbital is Denver_vanden_Eijkhof_Webpossibly the most commonly used, levetiracetam’s use is increasingly common due to its minimal adverse effects profile and usefulness as both a primary and adjuvant anti-epileptic drug (AED). A major drawback has been the need to administered orally 3 times daily in most animals. Recent data has suggested that extended release formulations of levetiracetam may be useful in cats dosed on a 24h basis. However, in some cats the chronic oral administration of any medication may not be possible or practical.

Transdermal drug administration is an increasingly popular method of drug delivery due to the ease of administration even to difficult-to-handle cats. Drawbacks include the variability in absorption and serum levels and difficulty predicting which drugs may be efficacious when administered this way. Phenobarbital has recently been shown to have transdermal bioavailability, albeit at the low end of therapeutic range. Levetiracetam is a small, water-soluble molecule with some lipophilic properties, making it a theoretical candidate for transdermal administration. 

The purpose of this study was to determine if transdermal administration of levetiracetam was able to attain therapeutic serum levels (5ug/mL) in healthy cats, with a secondary goal of measuring the stability of levetiracetam when compounded into a transdermal solution.

6 cats were enrolled in the study. All cats were domestic shorthairs with a median age of 3y. Cats were client owned and were clinically and neurologically healthy with normal PCV and serum biochemistry, and were not on any concurrent medications other than parasite prevention. Active drug was compounded into a commercial transdermal base (lipoderm gel) at 350 and 400mg/mL.

Samples of compounded drug were stored in a cool, dry location and analyzed for active drug content at 1, 3, and 5 weeks post compounding using spectrophotometry. A loss of 10% was noted in the 350mg/mL drug, and of 5% in the 400mg/mL drug over a 5w period.

Drug was applied to the inner surface of the pinna at 60mg/kg every 8h for 6 days. Drug was rubbed into the pinna until gel was no longer visible. On day 7, cats were admitted to hospital and blood collected at time 0, 0.5, 1, 2, 3, and 4 hours post dosing. Serum was analyzed for levetiracetam concentration, and drug was weaned to q12, then q24h before stopping to decrease the risk of withdrawal seizures.

Median drug concentrations were as follows: 0h: 16.1ug/mL ; 0.5h: 16.1ug/mL; 1h: 15.4ug/mL; 2h: 17.4ug/mL; 3h: 15.1ug/mL; 4h: 14.8ug/mL. Median drug concentration remained above the therapeutic level at all time points. Physical and neurologic exams remained normal.

The findings of this study suggest that transdermal levetiracetam is able to reach and maintain a therapeutic level, that there is stability of the drug in compounded solution, and that adverse effects are minimal. An obvious drawback to this study is the use of clinically normal cats- while in therapy the drug concentration is effective to control seizures, further work in epileptic animals would be recommended. It is also possible that, given the kinetics suggested, lower doses or greater dosing intervals may be effective. The authors suggest that cost for this method of administration may be prohibitive- 14 days of therapy with transdermal medication would cost ~54 times as much as oral tablets.  (MRK)

See Also

J A DG, Barnes Heller HL, Robertson M, L A T. Therapeutic serum phenobarbital concentrations obtained using chronic transdermal administration of phenobarbital in healthy cats. J Feline Med Surg. 2014;17(4):359‐363.

Carnes MB, Axlund TW, Boothe DM. Pharmacokinetics of levetiracetam after oral and intravenous administration of a single dose to clinically normal cats. Am J Vet Res. 2011;72(9):7‐12.

Lowrie M, Thomson S, Bessant C, Sparkes A, Harvey RJ, Garosi L. Levetiracetam in the management of feline audiogenic reflex seizures: a randomised, controlled, open‐label study. J Feline Med Surg. 2017;19(2):200‐206.

Epilepsy Keppra Transdermal

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