Abstract
Objective
To investigate pharmacokinetics (PK) of fentanyl administered by target-controlled
infusion (TCI), and to develop a PK model optimized by covariates for TCI in anaesthetized
dogs.
Study design
Prospective clinical study.
Animals
A group of 20 client-owned dogs with spinal pain undergoing anaesthesia for magnetic
resonance imaging.
Methods
Fentanyl was administered as an infusion to 20 anaesthetized dogs using a TCI system
incorporating a previously described fentanyl two-compartment PK. Arterial blood samples
were collected at specific time points during the infusion and over 60 minutes post-infusion
for measurement of fentanyl plasma concentrations. The predictive performance of the
Sano PK model was assessed by comparing predicted and measured plasma concentrations.
A population PK analysis was then performed using a nonlinear mixed-effect modelling
approach, allowing inter- and intra-individual variability estimation. Finally, a
quantitative stepwise evaluation of the influence of various covariates such as weight,
body condition score, size, size-related age, sex and type of premedication on the
PK model was considered.
Results
Overall predictive performance of the Sano PK set of variables was not clinically
acceptable in anaesthetized dogs. Fentanyl PK was best described by a three-compartment
model. Weight and sex were found to affect the volume of distribution of the central
compartment. Addition of these two covariate/variable associations resulted in a reduction
of the objective function value (OFV) from –340.18 to –448.34, and of the median population
weighted residual and the median population absolute weighted residual from 16.1%
and 38.6% to 3.9% and 20.3%, respectively. Fentanyl infusions at measured concentrations
up to 5.4 ng mL–1 in sevoflurane-anaesthetized dogs resulted in stable anaesthesia and smooth recoveries
without complications.
Conclusions and clinical relevance
A population three-compartment PK model for fentanyl TCI in anaesthetized dogs was
developed. Weight and sex have been detected and incorporated as significant covariates.
Keywords
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Article Info
Publication History
Published online: February 01, 2022
Accepted:
August 7,
2021
Received in revised form:
July 1,
2021
Received:
July 26,
2020
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2022 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.
