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

In healthy male cats, combining the sedative dexmedetomidine with vatinoxan and ketamine alters how the drugs move through the body. Vatinoxan increases the clearance of dexmedetomidine and reduces the bioavailability of intramuscular ketamine. Higher ketamine doses increase dexmedetomidine's central volume of distribution and improve intramuscular ketamine's bioavailability. Two-compartment models best described the time-plasma concentrations for all three drugs. The volume of distribution at steady state ranged from 1012 to 2429 mL/kg for dexmedetomidine, was 666 mL/kg for vatinoxan, and 2260 mL/kg for ketamine. Metabolic clearance was 12.5–15.4 mL/min/kg for dexmedetomidine, 3.7 for vatinoxan, and 23.8 for ketamine. Bioavailability for intramuscular and subcutaneous routes varied from 60% to 100%.

Study at a glance

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.