Oral Ketamine Lozenges Prove Impractical for Chronic Pain in Dogs with Osteoarthritis

A prospective, open-label clinical trial set out to test whether low-dose ketamine, given as an oral transmucosal gelatin lozenge every eight hours, could ease refractory chronic osteoarthritis pain in client-owned dogs. Instead, the study’s most consequential result was practical: caregivers and clinicians could reliably deliver the lozenge only about half the time, and enrollment had to be stopped early before efficacy could be assessed.

The trial enrolled nine dogs and measured administration success across 334 intended doses. Only 181 of those doses—54 percent—were successfully given in the lozenge formulation provided. That failure rate proved decisive. With so few participants remaining and dosing so inconsistent, the sample was too small for the intended statistical analysis of the study’s primary outcome, objective gait analysis of orthopedic function related to pain.

Before enrollment was halted, the researchers did collect pharmacokinetic data. Using liquid chromatography-tandem mass spectrometry, they quantified plasma ketamine and its metabolite norketamine at 30 and 60 minutes after lozenge administration in eight dogs. Mean ketamine concentrations were 4.5 ng/mL (plus or minus 3.0) at 30 minutes, falling to 1.7 ng/mL (plus or minus 1.2) at 60 minutes.

Norketamine told a different story. Mean plasma concentrations rose from 47 ng/mL (plus or minus 38.3) at 30 minutes to 65.7 ng/mL (plus or minus 46.7) at 60 minutes.

Those numbers come with important caveats. They are small-sample means with wide standard deviations, reported from an open-label trial in nine dogs, eight of whom contributed pharmacokinetic values. They describe absorption and metabolism, not pain relief. Because the efficacy analysis could not be performed, no conclusion can be drawn about whether transmucosal ketamine at 0.5 mg/kg reduces osteoarthritis pain or improves gait in these patients.

The pharmacokinetic profile itself also raises questions for any future efficacy work. Ketamine levels declined between the 30- and 60-minute measurements while norketamine climbed, a pattern consistent with rapid metabolism of the parent compound. Whether the concentrations achieved are sufficient for analgesic or other pharmacodynamic effects in dogs with chronic osteoarthritis pain remains untested and cannot be inferred from this trial.

The delivery problem was specific to the formulation tested. The gelatin lozenge, held in the mouth so the drug can cross the oral mucosa, proved difficult to administer in a real-world, client-owned setting—an environment where cooperative, repeated dosing every eight hours is essential. The authors conclude that an oral transmucosal gelatin lozenge is an impractical delivery method for low-dose ketamine in a clinical context.

The study team recommends evaluating alternative transmucosal ketamine formulations and conducting further research with an appropriately sized sample to assess efficacy, pharmacokinetics, and pharmacodynamics before the approach could be considered for clinical use. Until such studies are completed, the trial stands as a caution: a drug that is absorbed when it reaches the mucosa is of little value if the formulation cannot be delivered reliably to the patients who need it.

Subject of Research: Transmucosal ketamine delivery for chronic osteoarthritis pain in dogs

Article Title: Limitations of transmucosal ketamine administration for chronic pain in dogs with osteoarthritis

Article References: Seabolt, R. A., Elam, L. H., Griffenhagen, G. M., & Duerr, F. M. (2026). Limitations of transmucosal ketamine administration for chronic pain in dogs with osteoarthritis. Frontiers in Veterinary Science, 13, Article 1934484. https://doi.org/10.3389/fvets.2026.1934484

Image Credits: AI Generated

DOI: 10.3389/fvets.2026.1934484

Keywords: ketamine, dogs, osteoarthritis, chronic pain, transmucosal administration, pharmacokinetics, norketamine, veterinary medicine, clinical trial, drug delivery, Limitations, transmucosal