Pharmacokinetics of combinations of dexmedetomidine, vatinoxan and ketamine in male neutered cats.

OBJECTIVE

To characterize the pharmacokinetics of combinations of dexmedetomidine, vatinoxan and ketamine in cats.

STUDY

DESIGN

Partially randomized, crossover, experimental study.

ANIMALS: A group of six healthy male neutered cats, aged 1-2 years, weighing 5.4 ± 0.3 kg.

METHODS

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.

RESULTS

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.

CONCLUSIONS AND CLINICAL RELEVANCE: The pharmacokinetics of dexmedetomidine and the bioavailability of ketamine were affected by vatinoxan and the dose of ketamine.