Mirschberger Valentina, von Deimling Christian, Heider Anja, Spadavecchia Claudia, Rohrbach Helene, Zeiter Stephan
AO Research Institute Davos, 7270 Davos Platz, Switzerland.
Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, 7265 Davos Wolfgang, Switzerland.
Animals (Basel). 2020 Oct 1;10(10):1778. doi: 10.3390/ani10101778.
Transdermal patches allow a noninvasive and "stress free" analgesia in rabbits. As fentanyl uptake is dependent on exogenous and endogenous factors of the area where the patch is applied, this study investigated three different locations (neck, inner and outer surfaces of the ear) for fentanyl patch application to provide adequate and reliable fentanyl plasma concentrations above those previously shown to be analgesic. Fentanyl plasma concentration was measured at different time points (3, 6, 9, 12, 18, 24, 36, 48, 72, 96, 120 h) and rabbits were assessed for their general conditions and treatment-related side effects. Practicability of the proposed methods was evaluated. Following patch application on the neck, fentanyl plasma concentrations equal to or above the analgesic value were measured in all rabbits between 6 and 72 h. Comparable concentrations were reached between 9 and 48 h in all animals for the outer ear surface. However, for the inner ear surface, analgesic concentrations were not reached, even if practicability was considered the best for this location. Preparation of the neck skin was judged as the most cumbersome due to the clipping of the dense fur and patch removal resulted in erythema. In summary, the application of the fentanyl patch on the neck and outer ear surface allowed the reach of reliable plasma concentrations above the analgesic threshold in rabbits. When applied on the neck, fentanyl patches provided the longest duration of analgesic plasma concentrations, whereas patch application and removal were easier on the outer ear surface.
透皮贴剂可在兔身上实现无创且“无应激”的镇痛。由于芬太尼的吸收取决于贴剂所贴部位的外源性和内源性因素，本研究调查了芬太尼贴剂的三个不同贴敷部位（颈部、耳内外表面），以提供高于先前显示具有镇痛作用的足够且可靠的芬太尼血浆浓度。在不同时间点（3、6、9、12、18、24、36、48、72、96、120小时）测量芬太尼血浆浓度，并评估兔的一般状况和与治疗相关的副作用。评估了所提出方法的实用性。在颈部贴敷贴剂后，所有兔在6至72小时之间测得的芬太尼血浆浓度等于或高于镇痛值。对于耳外表面，所有动物在9至48小时之间达到了可比浓度。然而，对于内耳表面，即使认为该部位的实用性最佳，也未达到镇痛浓度。由于要剪掉浓密的毛发，颈部皮肤的准备被认为是最麻烦的，并且去除贴剂会导致红斑。总之，在兔的颈部和耳外表面贴敷芬太尼贴剂可使血浆浓度可靠地达到镇痛阈值以上。当贴敷在颈部时，芬太尼贴剂提供的镇痛血浆浓度持续时间最长，而在耳外表面贴敷和去除贴剂则更容易。
