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

Introduction This prospective, open-label clinical trial aimed to evaluate the efficacy of low-dose keta-mine (0.5 mg/kg) administered by oral transmucosal route every 8 h in client-owned dogs with refractory, chronic osteoarthritis pain. Methods Objective gait analysis was the primary outcome measure for orthopedic function relating to pain. Liquid chromatography-tandem mass spectrometry was used to quantify plasma ketamine and norketamine concentrations 30 and 60 min after administration of an oral transmucosal ketamine (TMK) gelatin lozenge. Results Enrollment was discontinued early due to difficulty of administering TMK in the formulation provided (administration success = 54%; 181/334 doses in n = 9 participants). The result-ing sample size was too small for the intended statistical analysis of objective outcome da-ta to determine treatment efficacy. Mean plasma concentrations of ketamine and norketa-mine ( n = 8 patients) were 4.5 ng/mL (+/− 3.0) and 47 ng/mL (+/− 38.3) at 30 min, and 1.7 ng/mL (+/− 1.2) and 65.7 ng/mL (+/− 46.7) at 60 min post administration. Discussion These values suggest that TMK is absorbed and subsequently metabolized into norketa-mine. However, the low success rate of administration demonstrated that an oral transmu-cosal gelatin lozenge is an impractical delivery method for low-dose ketamine in a clinical setting. Evaluation of alternative TMK formulations and further research with an appropriate sample size is recommended to evaluate efficacy, pharmacokinetics, and pharmacody-namics before TMK can be used clinically.