Paranjape Vaidehi V, Knych Heather K, Berghaus Londa J, Cathcart Jessica, Giancola Shyla, Craig Hannah, James Caroline, Saksena Siddharth, Reed Rachel A
Department of Small Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA, United States.
K. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.
Front Pain Res (Lausanne). 2024 Mar 11;5:1373555. doi: 10.3389/fpain.2024.1373555. eCollection 2024.
Matrix type transdermal buprenorphine patches have not been investigated in horses and may provide an effective means of providing continuous pain control for extended period and eliminating venous catheterization.
Assessment of the physiological variables (heart rate, respiratory rate, body temperature) and thermal nociceptive threshold testing, and describing the pharmacokinetic profile of transdermal buprenorphine matrix-type patch (20 μg h and 40 μg h dosing) in healthy adult horses.
Randomised experimental study with a Latin-square design.
Six adult healthy horses received each of the three treatments with a minimum 10 day washout period. BUP0 horses did not receive a patch (control). BUP20 horses received one patch (20 μg h) applied on the ventral aspect of the tail base resulting in a dose of 0.03-0.04 μg kg h. BUP40 horses received two patches placed alongside each other (40 μg h) on the tail base resulting in a dose of 0.07-0.09 μg kg h. Whole blood samples (for determination of buprenorphine concentration), physiological variables and thermal threshold testing were performed before (0 h) and at 2, 4, 8, 12, 16, 24, 32, 40, 48, 56, 64, 72, and 96 h after patch application. The patches were removed 72 h following placement and were analyzed for residual buprenorphine content.
Between the three groups, there was no change in physiological variables across timepoints as compared to baseline ( > 0.1). With the higher dose, there was a significant increase in thermal thresholds from baseline values from 2 h until 48 h and these values were significantly higher than the group receiving the lower patch dose for multiple timepoints up to 40 h. 40 μg h patch led to consistent measurable plasma concentrations starting at 2 h up to 96 h, with the mean plasma concentrations of > 0.1 ng/ml from 4 h to 40 h.
20 μg h and 40 μg h patch doses were well tolerated by all horses. At higher dose, plasma buprenorphine concentrations were more consistently measurable and blunted thermal thresholds for 48 h vs. 32 h with 20 μg h dosing as compared to control.
基质型丁丙诺啡透皮贴剂尚未在马匹中进行研究，它可能是一种提供长期持续疼痛控制并避免静脉置管的有效方法。
评估生理变量（心率、呼吸频率、体温）和热痛觉阈值测试，并描述健康成年马匹中丁丙诺啡基质型透皮贴剂（20μg/h和40μg/h剂量）的药代动力学特征。
采用拉丁方设计的随机实验研究。
6匹成年健康马匹接受三种治疗，每种治疗之间至少有10天的洗脱期。BUP0组马匹不接受贴剂（对照）。BUP20组马匹在尾根腹侧贴一片贴剂（20μg/h），剂量为0.03 - 0.04μg/kg/h。BUP40组马匹在尾根处并排贴两片贴剂（40μg/h），剂量为0.07 - 0.09μg/kg/h。在贴剂应用前（0小时）以及应用后2、4、8、12、16、24、32、40、48、56、64、72和96小时进行全血样本采集（用于测定丁丙诺啡浓度）、生理变量测量和热阈值测试。贴剂在放置72小时后取下，并分析其丁丙诺啡残留量。
与基线相比，三组之间各时间点的生理变量均无变化（P＞0.1）。使用较高剂量时，热阈值从基线值在2小时至48小时期间显著升高，并且在长达40小时的多个时间点，这些值显著高于接受较低贴剂剂量的组。40μg/h的贴剂在2小时至96小时期间导致血浆浓度持续可测，从4小时至40小时的平均血浆浓度＞0.1ng/ml。
所有马匹对20μg/h和40μg/h的贴剂剂量耐受性良好。与对照组相比，使用较高剂量时，血浆丁丙诺啡浓度更持续可测，并且热阈值在48小时内受到抑制，而20μg/h剂量时为32小时。
