Kaye Sarrah, Johnson Shawn, Arnold Robert D, Nie Ben, Davis Joshua T, Gulland Frances, Abou-Madi Noha, Fletcher Daniel J
J Zoo Wildl Med. 2016 Jun;47(2):438-46. doi: 10.1638/2015-0138.1.
ε-Aminocaproic acid (EACA) is a lysine analogue antifibrinolytic drug used to treat bleeding disorders in humans and domestic animals. Its use in zoological medicine is rare, and dosage is anecdotal. One possible application of EACA is to treat bleeding associated with prepatent Otostrongylus arteritis in Northern elephant seals ( Mirounga angustirostris ) presenting to wildlife rehabilitation centers. This study used an in vitro model of hyperfibrinolysis and a thromboelastograph-based assay to estimate the therapeutic plasma concentration of EACA in elephant seals (85 μg/ml, 95% confidence interval = 73.8-96.8 μg/ml). A concurrent pharmacokinetic study of orally administered, single-dose EACA found that doses of 75 and 100 mg/kg achieved therapeutic plasma concentrations (>85 μg/ml), but the drug was rapidly eliminated and remained in the therapeutic range for only 0.4 and 1.5 hr, respectively. Models of repeated oral dosing at 100 mg/kg every 6 hr predict that therapeutic plasma concentration will be maintained for 31.7% (7.6 hr) of a 24-hr period. More frequent dosing would be required to maintain continuous therapeutic concentrations but would be impractical in a wildlife rehabilitation setting. Further pharmacodynamic studies to evaluate the duration of action of EACA in elephant seals and a prospective, placebo-controlled study are needed to determine if EACA is effective in decreasing bleeding associated with prepatent Otostrongylus arteritis and other bleeding disorders in this species.
ε-氨基己酸(EACA)是一种赖氨酸类似物抗纤维蛋白溶解药物,用于治疗人类和家畜的出血性疾病。它在动物园医学中的应用很少,剂量也只是基于经验。EACA的一个可能应用是治疗在野生动物康复中心接受治疗的北象海豹(Mirounga angustirostris)潜在性耳圆线虫动脉炎相关的出血。本研究使用了高纤维蛋白溶解的体外模型和基于血栓弹力图的检测方法来估计象海豹体内EACA的治疗性血浆浓度(85μg/ml,95%置信区间=73.8-96.8μg/ml)。一项关于口服单剂量EACA的同时进行的药代动力学研究发现,75和100mg/kg的剂量可达到治疗性血浆浓度(>85μg/ml),但药物迅速消除,分别仅在治疗范围内维持0.4和1.5小时。每6小时以100mg/kg重复口服给药的模型预测,治疗性血浆浓度将在24小时周期内维持31.7%(7.6小时)。需要更频繁给药以维持持续的治疗浓度,但在野生动物康复环境中这是不切实际的。需要进一步的药效学研究来评估EACA在象海豹中的作用持续时间,以及一项前瞻性、安慰剂对照研究,以确定EACA是否能有效减少该物种潜在性耳圆线虫动脉炎和其他出血性疾病相关的出血。