Update (June 19, 2026): Zonisamide TDM Reference Interval 10-55 mcg/mL Proposed for Dogs in 207-Dog Cohort Study

TL;DR. Two 2024-2026 JVIM studies anchor the first evidence-based therapeutic drug monitoring reference interval for zonisamide in dogs (10-55 mcg/mL) and report 59-76% responder rates with monotherapy, providing a practical TDM framework for practitioners.

What just dropped

• Thungrat et al. 2026 (JVIM, open access; PMID 41742507) retrospectively analysed a 10-year TDM library from Auburn University spanning 207 dogs with non-structural epilepsy on zonisamide monotherapy. (https://europepmc.org/articles/PMC12881944)
  • 59% of dogs were responders (category 1+2 by IVETF criteria); 41% non-responders (P < .01).
  • Based on responders' plasma concentrations, a reference interval of 10-55 mcg/mL is proposed for dogs - broader than the human interval of 10-40 mcg/mL.
• Saito et al. 2024 (JVIM multicenter, open access; PMID 38780448) evaluated 56 newly-diagnosed, ASM-naive dogs in a prospective multicenter study. (https://europepmc.org/articles/PMC11256125)
  • 76% (40/53 evaluable) achieved >=50% seizure reduction; 55% (29/53) achieved seizure freedom over 12 weeks.
  • Mean trough ZNS concentration among responders: 18.9 mcg/mL (range 8.0-48.0 mcg/mL).
  • 7/56 (13%) experienced mild, transient AEs; no laboratory changes detected.

Context

Before these two studies, TDM for zonisamide in dogs lacked a validated reference interval, forcing practitioners to extrapolate from the human range. The proposed 10-55 mcg/mL canine interval accounts for species differences in pharmacokinetics and the IVETF-defined response criteria. Clinicians can use TDM to guide dose adjustments, particularly in non-responders or dogs showing signs of toxicity, while recognising that the retrospective design of the interval study means confidence intervals are wide.

What this changes in zonisamide-canine-epilepsy (https://www.thevoyage.ai/forvets/knowledge/zonisamide-canine-epilepsy)

The new proposed reference interval (10-55 mcg/mL) directly informs the TDM monitoring section of the zonisamide evergreen. The combination of prospective efficacy data (76% response rate) and a retrospective TDM dataset provides a more actionable clinical framework than previously available from extrapolated human data alone.

References

1. Thungrat K, Jukier T, Boothe DM. Efficacy of monotherapy with zonisamide and proposed reference interval in dogs with epilepsy: a cohort of 207 dogs (2011-2021). J Vet Intern Med. 2026;40(1):aalaf026. https://europepmc.org/articles/PMC12881944
2. Saito M, Nomura A, Hasegawa D, et al. Clinical efficacy and tolerability of zonisamide monotherapy in dogs with newly diagnosed idiopathic epilepsy. J Vet Intern Med. 2024;38(4):2228-2236. https://europepmc.org/articles/PMC11256125

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