Hallowell Kimberly L, Dembek Katarzyna, Horne Caitlyn R, Knych Heather K, Messenger Kristen M, Schnabel Lauren V
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, United States.
K. L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, CA, United States.
Front Vet Sci. 2024 May 15;11:1388470. doi: 10.3389/fvets.2024.1388470. eCollection 2024.
Steroid-associated laminitis remains a major concern with use of corticosteroids in horses. Individual case factors such as joint pathology, pre-existing endocrinopathies, or corticosteroid type, dose, and timing influencing steroid-induced laminitis risk have not been investigated. This study aimed to determine if systemic absorption of triamcinolone acetonide (TA) varies between intrasynovial (antebrachiocarpal) and extrasynovial (sacroiliac) injection sites, and to determine the effects of TA absorption on glucose, insulin, cortisol, and adrenocorticotropic hormone (ACTH). Twenty adult horses were randomized into antebrachiocarpal or sacroiliac joint injection groups, and each horse received bilateral injections with a total dose of 18 mg triamcinolone. Blood was collected prior to injection and at 1, 2, 4, 6, 8, 10, 12, 16, 20, 24, 36, 48, 60, and 72 h post-injection. Peak TA absorption occurred at 8 h in both groups, and was significantly higher in the intrasynovial group compared to the extrasynovial group (1.397 ng/mL, 0.672 ng/mL, < 0.05). Plasma TA levels were significantly higher in the intrasynovial group from 8 to 36 h post-injection ( < 0.05). There was no difference in glucose, insulin, cortisol, or ACTH between groups at any time point. Insulin and glucose were significantly increased from baseline at all timepoints from 10-72 h and 1-72 h post-injection, respectively. Horses with elevated baseline insulin values (>20 μU/mL) from both groups experienced a more marked hyperinsulinemia, reaching a mean peak insulin of 197.5 μU/mL as compared to 90.06 μU/mL in those with normal baseline insulin. Cortisol and ACTH were significantly decreased from baseline at timepoints from 4-72 h post-injection in both groups. This study is the first to evaluate drug absorption from the sacroiliac site and demonstrates that drug absorption varies between intrasynovial and extrasynovial injection sites. TA absorption causes metabolic derangements, most notably a marked hyperinsulinemia that is more severe in horses with elevated baseline insulin values. The influence of baseline endocrinopathies on response to corticosteroid administration as well as the effect of corticosteroid-induced metabolic derangements warrant further investigation as risk factors for corticosteroid-associated laminitis.
在马匹中使用皮质类固醇时，类固醇相关性蹄叶炎仍然是一个主要问题。尚未对诸如关节病理、既往内分泌疾病或影响类固醇诱导蹄叶炎风险的皮质类固醇类型、剂量和给药时间等个体病例因素进行研究。本研究旨在确定曲安奈德（TA）的全身吸收在滑膜内（腕掌关节）和滑膜外（骶髂关节）注射部位之间是否存在差异，并确定TA吸收对葡萄糖、胰岛素、皮质醇和促肾上腺皮质激素（ACTH）的影响。20匹成年马被随机分为腕掌关节或骶髂关节注射组，每匹马双侧注射，曲安奈德总剂量为18mg。在注射前以及注射后1、2、4、6、8、10、12、16、20、24、36、48、60和72小时采集血液。两组的TA吸收峰值均出现在8小时，滑膜内组的峰值显著高于滑膜外组（1.397ng/mL对0.672ng/mL，<0.05）。注射后8至36小时，滑膜内组的血浆TA水平显著更高（<0.05）。在任何时间点，两组之间的葡萄糖、胰岛素、皮质醇或ACTH均无差异。胰岛素和葡萄糖在注射后10至72小时和1至72小时的所有时间点分别较基线显著升高。两组中基线胰岛素值升高（>20μU/mL）的马匹出现更明显的高胰岛素血症，平均峰值胰岛素达到197.5μU/mL，而基线胰岛素正常的马匹为90.06μU/mL。两组在注射后4至72小时的时间点，皮质醇和ACTH较基线显著降低。本研究首次评估了骶髂关节部位的药物吸收情况，并表明滑膜内和滑膜外注射部位的药物吸收存在差异。TA吸收会导致代谢紊乱，最显著的是明显的高胰岛素血症，在基线胰岛素值升高的马匹中更为严重。作为类固醇相关性蹄叶炎的危险因素，基线内分泌疾病对皮质类固醇给药反应的影响以及皮质类固醇诱导的代谢紊乱的影响值得进一步研究。
