Pharmacokinetics of combinations of dexmedetomidine, vatinoxan and ketamine in male neutered cats.
Bruno H Pypendop, Yu Hong Law, Juhana Honkavaara, Linda S Barter
Veterinary anaesthesia and analgesia 2025 DOI: 10.1016/j.vaa.2025.01.015 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Partially randomized, crossover, experimental study Peer reviewed |
|---|---|
| Sample size | 6 |
| Population | Healthy male neutered cats aged 1-2 years weighing 5.4 ± 0.3 kg |
| Interventions | dexmedetomidine vatinoxan ketamine |
| Dose | dexmedetomidine 25 μg kg-1; vatinoxan 600 μg kg-1; ketamine 2.5 mg kg-1, 5 mg kg-1, or 10 mg kg-1 |
| Duration | 6 hours |
| Topics | Ketamine Esketamine |
| Keywords | Cats Dexmedetomidine Pharmacokinetics Vatinoxan Veterinary medicine Sedation drugs Feline pharmacology Anesthesia research Drug interactions |
| Key findings | Vatinoxan increases dexmedetomidine clearance and decreases intramuscular ketamine bioavailability, while higher ketamine doses increase dexmedetomidine's central volume of distribution and intramuscular ketamine bioavailability. |
Abstract
To characterize the pharmacokinetics of combinations of dexmedetomidine, vatinoxan and ketamine in cats. Partially randomized, crossover, experimental study. A group of six healthy male neutered cats, aged 1-2 years, weighing 5.4 ± 0.3 kg. Each cat was administered six treatments: dexmedetomidine (25 μg kg-1; D) + vatinoxan (600 μg kg-1; V) + ketamine (2.5 mg kg-1; K2.5) intramuscularly (IM) (DVK2.5IM); D + V + ketamine (5 mg kg-1; K5) IM (DVK5IM); D + V + ketamine (10 mg kg-1; K10) IM (DVK10IM); D + K5 IM (DK5IM); D + V + K5 subcutaneously (SC) (DVK5SC); or D + V + K5 intravenously (IV) (DVK5IV). Venous blood samples were collected before treatment injection, and at various times up to 6 hours thereafter. Plasma dexmedetomidine, vatinoxan and ketamine concentrations were measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-plasma dexmedetomidine, vatinoxan and ketamine data using nonlinear mixed effect modeling, including covariates for the effects of vatinoxan and the dose of ketamine where appropriate. Two-compartment models best fitted the time-plasma dexmedetomidine, vatinoxan and ketamine concentrations. The models predicted that vatinoxan increases the clearance of dexmedetomidine and decreases the bioavailability of IM ketamine and that increasing doses of ketamine increase the volume of the central compartment for dexmedetomidine and the bioavailability of IM ketamine. The volume of distribution at steady state (mL kg-1) and metabolic clearance (mL minute-1 kg-1) were 1012-2429 and 12.5-15.4 for dexmedetomidine, 666 and 3.7 for vatinoxan and 2260 and 23.8 for ketamine, respectively. Bioavailability (%) for IM and SC dexmedetomidine, vatinoxan and ketamine was 83 and 95, 99 and 95 and 60-100 and 100, respectively. The pharmacokinetics of dexmedetomidine and the bioavailability of ketamine were affected by vatinoxan and the dose of ketamine.
Comparable studies
Other randomized controlled trials on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community | 1994 | Randomized controlled trial | n = 19 |
| Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode | 2013 | Randomized controlled trial | n = 73 |
| Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery | 2005 | Randomized controlled trial | n = 75 |
| Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures | 2014 | Randomized controlled trial | n = 41 |
| Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers | 2000 | Single-blind placebo-controlled study | n = 20 |