Thomasy S M, Mama K R, Whitley K, Steffey E P, Stanley S D
K.L. Maddy Equine Analytical Chemistry Laboratory, California Animal Health and Food Safety Laboratory, School of Veterinary Medicine, University of California, Davis 95616, USA.
Equine Vet J. 2007 Jan;39(1):54-8. doi: 10.2746/042516407x153011.
In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined.
To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2.
A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry.
Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively.
Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.
为了评估芬太尼作为马匹吸入麻醉辅助药物的潜力，必须首先确定其药代动力学。
描述在治疗1中清醒的马匹和治疗2中用异氟烷麻醉的马匹静脉注射单剂量芬太尼后，芬太尼及其代谢产物N-[1-(2-苯乙基-4-哌啶基)马来酰苯胺酸（PMA）]的药代动力学。
采用平衡交叉设计（每组n = 4）。在治疗1期间，马匹接受单剂量芬太尼（4微克/千克体重，静脉注射），在治疗2期间，用异氟烷麻醉并维持在1.2倍最低肺泡麻醉浓度。经过30分钟的平衡期后，给每匹马静脉注射单剂量芬太尼（4微克/千克体重）。使用液相色谱-质谱法在不同时间点测量血浆芬太尼和PMA浓度。
异氟烷麻醉显著降低了芬太尼的平均清除率（P < 0.05）。清醒和麻醉马匹中芬太尼的消除半衰期分别为1小时，稳态分布容积分别为0.37和0.26升/千克体重。异氟烷麻醉还显著降低了PMA的表观清除率和分布容积。清醒和麻醉马匹中PMA的消除半衰期分别为2小时和1.5小时。
在用异氟烷麻醉的马匹中，芬太尼和PMA的药代动力学发生了显著改变。这些药代动力学参数为确定清醒和异氟烷麻醉马匹中合适的芬太尼负荷剂量和输注剂量提供了必要信息。
