Abstract
Chimpanzees are genetically and physiologically similar to humans. Several pharmacokinetic models of propofol are available and target controlled infusion (TCI) of propofol is established in humans, but not in chimpanzees. The purpose of this study was to investigate if human pharmacokinetic models can accurately predict propofol plasma concentration (Cp) in chimpanzees and if it is feasible to perform TCI in chimpanzees. Ten chimpanzees were anaesthetized for regular veterinary examinations. Propofol was used as an induction or maintenance agent. Blood samples were collected from a catheter in a cephalic vein at 3–7 time points between 1 and 100 min following the propofol bolus and/or infusion in five chimpanzees, or TCI in six chimpanzees. Cp was measured using high-performance liquid chromatography. The Marsh, Schnider and Eleveld human pharmacokinetic models were used to predict Cp for each case and we examined the predictive performances of these models using the Varvel criteria Median PE and Median APE. Median PE and Median APE for Marsh, Schnider and Eleveld models were within or close to the acceptable range. A human TCI pump was successfully maintained propofol Cp during general anesthesia in six chimpanzees. Human propofol pharmacokinetic models and TCI pumps can be applied in chimpanzees.
Highlights
Chimpanzees (Pan troglodytes) are the non-human primates which are physiologically and genetically most similar to humans, and their behavior and cognitive abilities have been intensively studied[1, 2]
In Japan, there were 302 chimpanzees in 48 institutions as of Dec. 20th 2020 (Great Ape Information Network, https://shigen.nig.ac.jp/gain/). They are no longer used in invasive studies, anesthesia is essential for regular and occasional veterinary examinations and treatments
If it is possible to use human propofol target controlled infusion (TCI) pumps in chimpanzees, it may facilitate the titration of propofol administration for general anesthesia and improve the quality of anesthesia as well as post anesthetic recovery
Summary
Chimpanzees (Pan troglodytes) are the non-human primates which are physiologically and genetically most similar to humans, and their behavior and cognitive abilities have been intensively studied[1, 2]. In Japan, there were 302 chimpanzees in 48 institutions as of Dec. 20th 2020 (Great Ape Information Network, https://shigen.nig.ac.jp/gain/). They are no longer used in invasive studies, anesthesia is essential for regular and occasional veterinary examinations and treatments. It is not possible to measure blood concentration of propofol in real time as it is for inhalation anesthetics. If it is possible to use human propofol TCI pumps in chimpanzees, it may facilitate the titration of propofol administration for general anesthesia and improve the quality of anesthesia as well as post anesthetic recovery. The objectives of this study were to investigate (1) if any of the human pharmacokinetic models could accurately predict chimpanzee plasma propofol concentration, and (2) if propofol TCI in chimpanzee is feasible using human TCI pumps
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