Thomasy S M, Slovis N, Maxwell L K, Kollias-Baker C
K.L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
J Vet Intern Med. 2004 Jul-Aug;18(4):550-4. doi: 10.1892/0891-6640(2004)18<550:tfcwna>2.0.co;2.
This study investigated the pharmcokinetics, efficacy, and safety of the fentanyl transdermal therapeutic system (TTS) in horses in which there was an inadequate analgesic response to nonsteroidal anti-inflammatory drugs (NSAIDs) alone. Nine horses with pain that was refractory to therapeutic doses of phenylbutazone (n = 3) or flunixin meglumine (n = 6) subsequently also received between 39 and 110 microg/kg of transdermal fentanyl. Blood samples were collected at 0, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 60, and 72 hours after patch application, and a radioimmunoassay was used to determine serum fentanyl concentrations. Pharmacokinetic values were determined by noncompartmental analysis. Physical examination findings were recorded in all horses, and pain and lameness grading systems were used to assign scores to 8 and 6 horses, respectively. All horses tolerated the administration of fentanyl TTS, in that no clinically significant adverse effects attributable to fentanyl were observed. Use of the TTS resulted in variable serum concentrations of fentanyl, with a peak serum concentration of 2.2+/-1.1 ng/mL (mean+/-SD) and a time to peak serum concentration of 26+/-13 hours. After transdermal fentanyl administration, mean time to reach serum fentanyl concentrations consistent with analgesia in other species (1 ng/mL) was 14 hours. In addition, serum fentanyl concentrations of 1 ng/mL or greater were maintained in all but one horse for at least 18 hours. Pain scores were significantly decreased after fentanyl TTS and NSAID administration (P < .05), but lameness scores were not significantly different (P > .05). Overall, administration of fentanyl TTS had a favorable pharmacokinetic profile in horses with clinical pain, and the fentanyl TTS in combination with NSAIDs appeared to provide safe and effective analgesia in most of the horses with pain that was refractory to NSAID therapy alone.
本研究调查了芬太尼透皮治疗系统(TTS)在对非甾体抗炎药(NSAIDs)单独镇痛反应不足的马匹中的药代动力学、疗效和安全性。9匹对治疗剂量的苯基丁氮酮(n = 3)或氟尼辛葡甲胺(n = 6)难治性疼痛的马匹随后也接受了39至110微克/千克的透皮芬太尼。在贴剂应用后0、1、2、3、4、5、6、12、24、36、48、60和72小时采集血样,并用放射免疫分析法测定血清芬太尼浓度。通过非房室分析确定药代动力学值。记录所有马匹的体格检查结果,分别使用疼痛和跛行分级系统对8匹和6匹马进行评分。所有马匹均耐受芬太尼TTS的给药,未观察到可归因于芬太尼的临床显著不良反应。使用TTS导致芬太尼血清浓度变化,血清峰值浓度为2.2±1.1纳克/毫升(平均值±标准差),血清峰值浓度出现时间为26±13小时。透皮给予芬太尼后,达到与其他物种镇痛一致的血清芬太尼浓度(1纳克/毫升)的平均时间为14小时。此外,除一匹马外,所有马匹的血清芬太尼浓度至少维持在1纳克/毫升或更高水平达18小时。芬太尼TTS和NSAIDs给药后疼痛评分显著降低(P < 0.05),但跛行评分无显著差异(P > 0.05)。总体而言,芬太尼TTS给药在患有临床疼痛的马匹中具有良好的药代动力学特征,芬太尼TTS与NSAIDs联合使用似乎能为大多数对单独NSAID治疗难治性疼痛的马匹提供安全有效的镇痛作用。