This week’s TidBit is a good one! At the beginning of 2026 an article was published in the Journal of Veterinary Internal Medicine by Drs. Thungrat, Jukier and Boothe in which the authors outlined a possible therapeutic range for Zonisamide in dogs. That’s right, they are suggesting a CANINE specific reference interval! Here’s how they did it…
This study was a retrospective evaluation of the records of 207 dogs with non-structural epilepsy (it’s not clear if this was confirmed). The dogs were categorized into one of three groups according to their seizure response after starting zonisamide: 1) seizure freedom, 2) partial success or 3) uncontrolled.
Seizure freedom – a greater than 3x fold increase in interictal period compared to pre-treatment, or at least 3 months between seizures. (ex: seizures occurred in January, February and March pre-treatment and May and September post treatment. Pre-treatment interictal period was 1 month; post-treatment was 4 months.)
Partial success – seizures were considered reduced in frequency, severity and/or cluster prevention. The authors didn’t detail that a 50% reduction was indicated for this category, however that is typically what is considered partial success.
Uncontrolled – no improvement noted on treatment
Dogs were administered zonisamide for at least 3 months and had TDM performed after a minimum of 10 days on medication.
Results
Category 1: 60 dogs (29%) met these criteria.
Category 2: 63 dogs (30%) met these criteria
Category 3: 84 (41%) of dogs met these criteria
The authors then bundled the category 1 and category 2 dogs into one category and referred to these as responders (123/207 dogs: 59%). They stated that when evaluating responders vs non-responders, a reference interval (RI) of 10-55 ug/ml became evident. The human reference interval is 10-40 ug/ml, so this is an even wider RI than previously used (if you used one). It makes me nervous to use an extremely wide RI, but over time we may be able to more closely define the appropriate window. For example, phenobarbital’s RI is 15-40 ug/ml for most labs. However, most neurologists use 25-30 ug/ml as a target RI because many patients aren’t controlled at drug concentrations less than 20 ug/ml, and drug concentrations higher than 30 ug/ml, while often effective, may result in undesirable toxicity. Something similar may become evident for zonisamide with time. As with all TDM – stay tuned for more information!
Also, it’s important to note that 59% of dogs in this study were considered responders. This means that less than 60% of dogs that receive this medication as monotherapy demonstrated improved seizure control. These numbers are similar to a prior study that noted 76% of dogs receiving zonisamide were responders. Compared to phenobarbital (76-90%) and bromide (55-95%), zonisamide does not appear to have as robust control.
Key points
If you place a dog on zonisamide, it is appropriate to measure zonisamide serum drug concentrations after 14 days. Serum can be sent to the Auburn Pharmacology Lab.
Zonisamide is an appropriate AED for monotherapy or add on therapy. Seizure control may be similar or less effective as phenobarbital and bromide.
Zonisamide is a sulfa-derivative so use carefully in patients with sulfa sensitivity.