Population analysis to assess the influence of age and body weight on pharmacokinetics and pharmacodynamics of dexmedetomidine in New Zealand White rabbits.

OBJECTIVES To develop population pharmacokinetic (PK) and pharmacodynamic (PD) model of dexmedetomidine in New Zealand White rabbits and investigate the influence of animals' age and weight on the model parameters. To assess the linearity of pharmacokinetics of the drug in the examined dose range. STUDY DESIGN Prospective, crossover study. ANIMALS A total of 18 New Zealand White rabbits. METHODS Dexmedetomidine was administered as a single intravenous bolus injection in the doses from 25 µg kg-1 to 300 µg kg-1 . Each New Zealand White rabbit was given the same dose of drug in its three developmental stages. To determine dexmedetomidine PK, seven blood samples were taken from each animal. Pedal withdrawal reflex was the PD response used to assess the degree of sedation. Nonlinear mixed effects modelling was used for the population PK/PD analysis. RESULTS The typical value of elimination clearance was 0.061 L minute-1 and was 35 % higher in younger New Zealand White rabbits compared to older animals. The PK of dexmedetomidine was linear in the examined concentration range. The age-related changes in sensitivity to dexmedetomidine were not detected. CONCLUSIONS AND CLINICAL RELEVANCE The results suggest that due to pharmacokinetic reason younger animals will have lower dexmedetomidine concentrations and shorter duration of sedation than older animals for the same doses of dexmedetomidine per kg of body weight. This article is protected by copyright. All rights reserved.