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Population analysis to assess the influence of age and body weight on pharmacokinetics and pharmacodynamics of dexmedetomidine in New Zealand White rabbits
Author(s) -
Warzybok Justyna,
Bienert Agnieszka,
BorsukDe Moor Agnieszka,
Płotek Włodzimierz,
Kulińska Karolina,
Czerniak Katarzyna,
Billert Hanna,
Klupczyńska Agnieszka,
Matysiak Jan,
Grześkowiak Edmund,
Wiczling Paweł
Publication year - 2020
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2248
Subject(s) - pharmacokinetics , dexmedetomidine , pharmacodynamics , sedation , medicine , crossover study , population , body weight , bolus (digestion) , nonmem , anesthesia , pharmacology , zoology , biology , environmental health , alternative medicine , pathology , placebo
The purpose of this work was i) to develop a population pharmacokinetic (PK) and pharmacodynamic (PD) model of dexmedetomidine (DEX) in New Zealand White rabbits, ii) to investigate the influence of the age and weight of the animals on the model parameters, and iii) to assess the linearity of DEX PKs in the examined dose range. This was a prospective, crossover study, using a total of 18 New Zealand White rabbits. DEX was administered as a single intravenous bolus injection in the doses from 25 to 300 μg kg −1 . Each New Zealand White rabbit was given the same dose of drug in its three developmental stages. To determine the DEX PK, seven blood samples were taken from each animal. The 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. The typical value of elimination clearance was 0.061 L min −1 and was 35% higher in younger New Zealand White rabbits compared with older animals. The PK of DEX was linear in the examined concentration range. Age‐related changes in sensitivity to DEX were not detected. The results suggest that due to the pharmacokinetics, younger animals will have lower DEX concentrations and a shorter duration of sedation than older animals given the same doses of DEX per kg of body weight.