Division of Veterinary Anesthesiology, Department of Clinical Veterinary Medicine, Vetsuisse Faculty, University of Bern, 3001 Bern, Switzerland.
Res Vet Sci. 2010 Jun;88(3):512-8. doi: 10.1016/j.rvsc.2009.12.004. Epub 2010 Jan 6.
The objective of this study was to assess a pharmacokinetic algorithm to predict ketamine plasma concentration and drive a target-controlled infusion (TCI) in ponies. Firstly, the algorithm was used to simulate the course of ketamine enantiomers plasma concentrations after the administration of an intravenous bolus in six ponies based on individual pharmacokinetic parameters obtained from a previous experiment. Using the same pharmacokinetic parameters, a TCI of S-ketamine was then performed over 120 min to maintain a concentration of 1 microg/mL in plasma. The actual plasma concentrations of S-ketamine were measured from arterial samples using capillary electrophoresis. The performance of the simulation for the administration of a single bolus was very good. During the TCI, the S-ketamine plasma concentrations were maintained within the limit of acceptance (wobble and divergence <20%) at a median of 79% (IQR, 71-90) of the peak concentration reached after the initial bolus. However, in three ponies the steady concentrations were significantly higher than targeted. It is hypothesized that an inaccurate estimation of the volume of the central compartment is partly responsible for that difference. The algorithm allowed good predictions for the single bolus administration and an appropriate maintenance of constant plasma concentrations.
本研究旨在评估一种预测氯胺酮血浆浓度的药代动力学算法，并驱动小马的靶控输注（TCI）。首先，该算法用于根据先前实验中获得的个体药代动力学参数模拟六匹小马静脉推注后氯胺酮对映体血浆浓度的过程。然后，使用相同的药代动力学参数，对 S-氯胺酮进行 120 分钟的 TCI，以维持血浆中 1μg/mL 的浓度。使用毛细管电泳从动脉样本中测量实际的 S-氯胺酮血浆浓度。单次推注给药的模拟性能非常好。在 TCI 期间，S-氯胺酮的血浆浓度在初始推注后达到峰值浓度的 79%（IQR，71-90）的范围内波动和发散<20%，保持在可接受的范围内。然而，在三匹小马中，稳定浓度明显高于目标浓度。据推测，中央隔室体积的不准确估计部分导致了这种差异。该算法允许对单次推注给药进行良好的预测，并适当维持恒定的血浆浓度。
