Primate Research Institute, Kyoto University, Inuyama, Aichi, Japan.
Chubu Gakuin University, Seki, Gifu, Japan.
Sci Rep. 2021 Jan 13;11(1):1214. doi: 10.1038/s41598-020-79914-7.
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.
黑猩猩在基因和生理上与人类相似。已有几种丙泊酚的药代动力学模型,丙泊酚的靶控输注(TCI)在人类中建立,但在黑猩猩中尚未建立。本研究旨在探讨人类药代动力学模型是否能准确预测黑猩猩丙泊酚血浆浓度(Cp),以及在黑猩猩中进行 TCI 是否可行。10 只黑猩猩接受常规兽医检查麻醉。丙泊酚用作诱导或维持药物。在 5 只黑猩猩中,在给予丙泊酚推注和/或输注后 1 至 100 分钟内,从头静脉的导管中采集了 3-7 个时间点的血液样本,或在 6 只黑猩猩中进行 TCI。使用高效液相色谱法测量 Cp。使用 Marsh、Schnider 和 Eleveld 三种人类药代动力学模型来预测每个案例的 Cp,并使用 Varvel 标准的 Median PE 和 Median APE 来检查这些模型的预测性能。Marsh、Schnider 和 Eleveld 模型的 Median PE 和 Median APE 在可接受范围内或接近可接受范围。在六只黑猩猩的全身麻醉期间,人类 TCI 泵成功维持了丙泊酚 Cp。人类丙泊酚药代动力学模型和 TCI 泵可应用于黑猩猩。