Plasma concentrations of buprenorphine administered via matrix-type transdermal patches applied at three different anatomical locations in healthy adult horses.

IF 2.5 Q2 CLINICAL NEUROLOGY Frontiers in pain research (Lausanne, Switzerland) Pub Date : 2024-06-19 eCollection Date: 2024-01-01 DOI:10.3389/fpain.2024.1390322
Vaidehi V Paranjape, Heather K Knych, Londa J Berghaus, Shyla Giancola, Jessica Cathcart, Rachel A Reed
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Abstract

Background: Anatomical location-dependent differences in transdermal opioid penetration are well described in human patients. Although this has been investigated in horses with fentanyl, there is no literature available on location-dependent plasma buprenorphine concentrations when administered as a transdermal matrix-type patch.

Objective: This study aims to compare the plasma concentrations achieved from the matrix-type transdermal buprenorphine patches placed at different anatomical sites (metacarpus, gaskin, and ventral tail base) in healthy adult horses.

Study design: This is a randomized experimental study with a Latin square design.

Methods: Six adult horses were given each of three treatments with a minimum 10-day washout period. For each treatment, two 20 μg h-1 matrix-type buprenorphine patches were applied to the ventral aspect of the tail base (TailTDP), metacarpus region (MetacarpusTDP), or gaskin region (GaskinTDP). Whole blood samples (for determination of buprenorphine concentration) and physiological variables were collected before (0 h) and at 0.5, 2, 4, 6, 8, 10, 12, 16, 24, 32, 48, 56, 72, 96 and 120 h after patches were applied. The patches were removed 96 h following placement and were analyzed for residual buprenorphine content. Buprenorphine concentrations were measured in plasma by LC-MS/MS. A mixed-effects model was used to analyze the physiological variables.

Results: Between the three treatment groups, there was no change in physiological variables across timepoints as compared to baseline and when compared to each other in a single horse and between horses (p > 0.3). When comparing all three locations, the buprenorphine uptake was observed to be more consistent with respect to measurable plasma concentrations >0.1 ng ml-1 when applied to the ventral aspect of the tail base. In the TailTDP group, the mean plasma buprenorphine concentrations were >0.1 ng ml-1 from 2 to 32 h. The highest group mean was 0.25 ng ml-1 noted at 4 h.

Conclusions: The metacarpal and gaskin regions presented more erratic and inconsistent buprenorphine uptake and plasma concentrations as compared to the ventral aspect of the tail base. Further research must be directed at investigating the optimal dose, achievable duration of analgesia, change in measurable plasma concentrations, and behavioral and systemic effects.

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在健康成年马的三个不同解剖位置通过基质型透皮贴片给药丁丙诺啡的血浆浓度。
背景:在人类患者中,透皮阿片类药物渗透性的解剖位置依赖性差异已得到充分描述。虽然在马匹身上用芬太尼进行过研究,但目前还没有文献报道以透皮基质型贴片形式给药时,丁丙诺啡的血浆浓度与位置有关:本研究旨在比较在健康成年马的不同解剖部位(掌骨、加斯金和腹侧尾根)贴上基质型透皮丁丙诺啡贴片后的血浆浓度:研究设计:这是一项采用拉丁方阵设计的随机实验研究:方法:六匹成年马分别接受三种治疗,每种治疗至少有 10 天的冲洗期。每种治疗均在马尾基部腹侧(TailTDP)、掌骨区(MetacarpusTDP)或胫骨区(GaskinTDP)贴上两片20微克/小时的基质型丁丙诺啡贴片。在贴片前(0 小时)和贴片后 0.5、2、4、6、8、10、12、16、24、32、48、56、72、96 和 120 小时收集全血样本(用于测定丁丙诺啡浓度)和生理变量。贴片贴上 96 小时后取下,分析残留的丁丙诺啡含量。通过 LC-MS/MS 测定血浆中丁丙诺啡的浓度。采用混合效应模型分析生理变量:在三个治疗组之间,各时间点的生理变量与基线相比没有变化,单匹马之间以及马匹之间的生理变量也没有变化(P > 0.3)。在对所有三个位置进行比较时,发现在尾基部腹侧使用丁丙诺啡时,可测量的血浆浓度大于 0.1 毫微克/毫升-1。在 TailTDP 组中,从 2 到 32 小时,平均血浆丁丙诺啡浓度都大于 0.1 纳克毫升-1。4 小时时,该组的平均浓度最高,为 0.25 纳克毫升/升:结论:与尾基部腹侧相比,掌骨和胫骨区域的丁丙诺啡吸收和血浆浓度更不稳定和不一致。必须针对最佳剂量、可达到的镇痛持续时间、可测量的血浆浓度变化以及行为和全身效应开展进一步研究。
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