Hart Kelsey A, Dirikolu Levent, Ferguson Duncan C, Norton Natalie A, Barton Michelle H
Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Am J Vet Res. 2012 Jan;73(1):68-75. doi: 10.2460/ajvr.73.1.68.
To compare daily endogenous cortisol production rate and the pharmacokinetics of an i.v. bolus of hydrocortisone between neonatal foals and adult horses.
10 healthy full-term 2- to 4-day-old foals and 7 healthy adult horses.
Blood samples were collected from each horse every 15 to 20 minutes for 24 hours for determination of 24-hour mean cortisol concentration. Afterward, dexamethasone (0.08 mg/kg) was administered i.v. to suppress endogenous cortisol production. Twelve hours afterward, hydrocortisone sodium succinate (1.0 mg/kg) was administered as a rapid i.v. bolus and serial blood samples were collected to determine hydrocortisone pharmacokinetics. Cortisol concentrations, daily cortisol production rate, and hydrocortisone pharmacokinetics were determined, and results were compared between adult horses and foals.
The mean ± SD 24-hour cortisol concentration was significantly lower in foals (20 ± 4 ng/mL) than in horses (26 ± 6 ng/mL), but the daily cortisol production rate was significantly greater in foals (6,710 ± 320 ng/kg/d) than in horses (2,140 ± 400 ng/kg/d). For hydrocortisone, foals had a significantly greater volume of distribution at steady state (1.92 ± 1.11 L/kg) and total body clearance (1.39 ± 0.108 L/kg/h) and significantly lower peak plasma concentration (1,051 ± 343 ng/mL) than did horses (0.58 ± 0.15 L/kg, 0.349 ± 0.065 L/kg/h, and 8,934 ± 3,843 ng/mL, respectively).
Important differences were detected in cortisol production and metabolism between neonatal foals and adult horses consistent with lower plasma protein binding of cortisol in foals. This decrease may contribute to cortisol insufficiency during prolonged critical illness in neonatal foals.
比较新生马驹和成年马每日内源性皮质醇生成率以及静脉注射氢化可的松的药代动力学。
10匹健康足月2至4日龄马驹和7匹健康成年马。
每15至20分钟从每匹马采集血样，持续24小时，以测定24小时平均皮质醇浓度。之后，静脉注射地塞米松（0.08mg/kg）以抑制内源性皮质醇生成。12小时后，快速静脉推注琥珀酸钠氢化可的松（1.0mg/kg），并采集系列血样以测定氢化可的松药代动力学。测定皮质醇浓度、每日皮质醇生成率和氢化可的松药代动力学，并比较成年马和马驹的结果。
马驹的平均±标准差24小时皮质醇浓度（20±4ng/mL）显著低于成年马（26±6ng/mL），但马驹的每日皮质醇生成率（6710±320ng/kg/d）显著高于成年马（2140±400ng/kg/d）。对于氢化可的松，马驹在稳态时的分布容积（1.92±1.11L/kg）和全身清除率（1.39±0.108L/kg/h）显著高于成年马，而血浆峰浓度（1051±343ng/mL）显著低于成年马（分别为0.58±0.15L/kg、0.349±0.065L/kg/h和8934±3843ng/mL）。
新生马驹和成年马在皮质醇生成和代谢方面存在重要差异，这与马驹皮质醇的血浆蛋白结合较低一致。这种降低可能导致新生马驹在长期危重病期间出现皮质醇不足。
