Sano Tadashi, Nishimura Ryohei, Kanazawa Hideko, Igarashi Eri, Nagata Yoshiko, Mochizuki Manabu, Sasaki Nobuo
Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
Vet Anaesth Analg. 2006 Jul;33(4):266-73. doi: 10.1111/j.1467-2995.2005.00266.x.
To determine the plasma concentration and define the pharmacokinetic characteristics of fentanyl (10 microg kg(-1)) administered as a single intravenous (IV) injection followed by: (a) no further drug; or (b) a constant rate infusion (CRI) of fentanyl 10 microg kg(-1) hour(-1) lasting 1, 3 or 4 hours in dogs. Animals Fourteen healthy adult beagles (seven males and seven females).
Randomized cross-over design.
Dogs were randomly assigned to four treatment groups. Drugs were administered to each dog in a randomized cross-over design with at least a 14-day washout interval between experiments. All dogs received an IV loading dose of fentanyl (10 microg kg(-1)). One group received no further fentanyl. In others, the loading dose was followed by a CRI of fentanyl (10 microg kg(-1) hour(-1)) for 1, 3 or 4 hours. Blood samples were collected and plasma fentanyl concentrations determined using high-performance liquid chromatography-mass spectrometry. Plasma pharmacokinetic estimates were obtained by plotting plasma concentrations versus time data and by fitting the change in concentration to a pharmacokinetic model, using a purpose-built program written by the Graduate School of Pharmaceutical Sciences (Kyoto University) in Visual Basic (VBA) on Excel (Microsoft Corporation).
Plasma fentanyl concentration decreased rapidly after single IV injection: the plasma concentration-time curve best fitted a two-compartment model. Pharmacokinetic variables for IV injection were characterized by a short distribution half-time (t1/2alpha was 4.5 minutes), a relatively long elimination half time (t1/2beta was 45.7 minutes), a large volume of distribution (approximately 5 L kg(-1)) and high total body clearance (77.9 mL minute(-1) kg(-1)). Stable plasma fentanyl levels were obtained in all CRI groups although pharmacokinetic variables were influenced by the duration of administration.
While this study clarified the pharmacokinetic features of rapid IV fentanyl injection and CRI in dogs, the plasma concentration achieving analgesia was not and so further research is needed. Further studies on the effects of other sedatives and/or anaesthetics on fentanyl's disposition are also required as the drug is commonly used with other agents.
确定单次静脉注射（IV）给予芬太尼（10微克/千克）后，在以下两种情况下的血浆浓度并明确其药代动力学特征：（a）不再给予其他药物；或（b）以10微克/千克·小时⁻¹的恒速输注（CRI）持续1、3或4小时，研究对象为犬。动物 14只健康成年比格犬（7只雄性和7只雌性）。
随机交叉设计。
将犬随机分为四个治疗组。采用随机交叉设计对每只犬给药，实验之间至少间隔14天的洗脱期。所有犬均接受静脉注射负荷剂量的芬太尼（10微克/千克）。一组不再给予芬太尼。其他组在负荷剂量后给予芬太尼的CRI（10微克/千克·小时⁻¹），持续1、3或4小时。采集血样，使用高效液相色谱 - 质谱法测定血浆芬太尼浓度。通过绘制血浆浓度与时间数据图，并使用京都大学药学院用Visual Basic（VBA）在Excel（微软公司）上编写的专用程序将浓度变化拟合到药代动力学模型，获得血浆药代动力学估计值。
单次静脉注射后血浆芬太尼浓度迅速下降：血浆浓度 - 时间曲线最适合二室模型。静脉注射的药代动力学变量的特征为分布半衰期短（t1/2α为4.5分钟）、消除半衰期相对较长（t1/2β为45.7分钟）、分布容积大（约5升/千克）和全身清除率高（77.9毫升/分钟·千克）。尽管药代动力学变量受给药持续时间影响，但所有CRI组均获得了稳定的血浆芬太尼水平。
虽然本研究阐明了犬快速静脉注射芬太尼和CRI的药代动力学特征，但未明确达到镇痛效果的血浆浓度，因此需要进一步研究。由于该药物常与其他药物联合使用，还需要进一步研究其他镇静剂和/或麻醉剂对芬太尼处置的影响。
