January 29, 2019

Testing Transdermal Phenobarbital in Cats

A recent study at Washington State University examined a new route of administration for the popular anti-seizure drug.
 
By Natalie Stilwell, DVM, MS, PhD
Phenobarbital is a popular, first-line barbiturate for the treatment of seizure disorders in dogs and cats. Parenteral and oral formulations are currently used in companion animal species.

Researchers at Washington State University recently tested a transdermal phenobarbital formulation, with the goal of establishing a low-stress, safe, and effective administration route for feline patients and their owners. 

Methods
Transdermal phenobarbital was assessed in 6 healthy, client-owned cats ranging in age from 1 to 15 years and weighing 3 to 6 kg. The drug was compounded in a pluronic lecithin organogel (PLO)–based vehicle in concentrations of 120 to 180 mg/mL. A 0.1-mL volume of gel was applied to the inner pinna of each ear to deliver a dose of 6.0 to 6.4 mg/kg to each cat. The drug was administered every 12 hours for 14 days. Owners were instructed to apply the dose to the pinna with a gloved finger and to remove any remaining medication with a gloved finger before applying the next dose.

On alternating days throughout the study, blood samples were collected for serum phenobarbital measurement 3 to 6 hours after dosing, and cats were monitored for adverse effects. Complete blood cell count, chemistry, and bile acids assay were performed at the beginning and end of the study. Also, owners completed a questionnaire at the end of the study to assess pet behavior throughout the study and perception of various drug administration routes.

Results
Transdermal phenobarbital application resulted in a mean peak drug concentration of 5.94 μg/mL in serum, which occurred an average of 13.3 days into the study. However, concentrations fell short of the target therapeutic range of 15 to 45 μg/dL.

No significant adverse effects were reported from transdermal phenobarbital administration, although mild erythema or excoriation of the pinnae was noted in 3 cats during the study. Also, mild hyperglobulinemia and mildly increased alanine aminotransferase were each reported in 1 cat during the study. Preprandial and postprandial bile acids were normal in all cats at the end of the study.

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Half of the owners completed the questionnaire. Although they reported that their cats tolerated transdermal medication well, 1 owner noted that the cat began hiding when approached. Two of 3 owners generally preferred transdermal drug administration over the oral route, although all owners noted that the gel was relatively dry, frequently fell off after administration, and left a flaky residue on the pinna after application.

Potency tests performed for 3 of the 6 compounded phenobarbital gels found a wide range of potencies ranging from 63% to 82%.

Conclusions
Transdermal application of phenobarbital led to detectable serum drug concentrations; however, the investigators cited high variations in compounded drug potency and gel consistency as the main reasons for the observed subtherapeutic results. They indicated a continued need for research on appropriate drug vehicles and formulations for the cat.

Nevertheless, the drug was well tolerated by patients and caused only minor adverse effects. Also, most participating owners reported they would prefer transdermal to oral medications for their pet cats in the future.

Dr. Stilwell provides freelance medical writing and aquatic veterinary consulting services through her business, Seastar Communications and Consulting. In addition to her DVM obtained from Auburn University, she holds a MS in fisheries and aquatic sciences and a PhD in veterinary medical sciences from the University of Florida.


 

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