Alwood Amy J, Downend Amanda B, Brooks Marjory B, Slensky Kimberly A, Fox Julia A, Simpson Stephen A, Waddell Lori S, Baumgardner James E, Otto Cynthia M
Department of Clinical Studies Philadelphia, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA.
J Vet Intern Med. 2007 May-Jun;21(3):378-87. doi: 10.1892/0891-6640(2007)21[378:aeolhi]2.0.co;2.
Low-molecular-weight heparin (LMWH) has potential benefit in cats at risk for thromboembolic disease. However, LMWH pharmacokinetics has not been characterized in the cat. Drug effect with LMWH may be evaluated with analysis of factor Xa inhibition (anti-Xa) or thromboelastography (TEG).
Administration of LMWH at previously recommended dosages and schedules to healthy cats will result in inhibition of factor Xa and hypocoagulable TEG.
In vivo research with heparin was performed in 5 purpose-bred cats.
In a prospective study with randomized crossover design, heparin or placebo was administered. Treatments were unfractionated heparin (UFH), 250 IU/kg q6h; dalteparin, 100 IU/kg q12h; enoxaparin, 1 mg/kg q12h; or 0.9% saline, 0.25 mL/kg q6h. Each drug was administered for 5 consecutive days followed by a minimum washout of 14 days. Baseline and post-treatment analyses included anti-Xa, TEG, and prothrombin time/activated partial thromboplastin time.
Mean anti-Xa activity 4 hours after enoxaparin (0.48 U/mL) approached the human therapeutic target (0.5-1.0 U/mL); however, mean trough anti-Xa activity was below detection limits. Mean anti-Xa activity 4 hours after dalteparin was lower, and only 1 cat attained therapeutic target at a single time point. Cats receiving UFH attained target anti-Xa activity and changes in TEG at trough and 4 hours.
Cats have rapid absorption and elimination kinetics with LMWH therapy. On the basis of pharmacokinetic modeling, cats will require higher dosages and more frequent administration of LMWH to achieve human therapeutic anti-factor Xa activity of 0.5-1 U/mL. Peak anti-Xa activity is predicted at 2 hours after administration of LMWH.
低分子量肝素（LMWH）对有血栓栓塞性疾病风险的猫可能有益。然而，LMWH在猫体内的药代动力学尚未得到明确。LMWH的药物作用可通过分析Xa因子抑制（抗Xa）或血栓弹力图（TEG）来评估。
以先前推荐的剂量和给药方案给健康猫施用LMWH将导致Xa因子受到抑制且TEG出现低凝状态。
对5只专门培育的猫进行了肝素的体内研究。
在一项采用随机交叉设计的前瞻性研究中，施用肝素或安慰剂。治疗药物为普通肝素（UFH），250 IU/kg，每6小时一次；达肝素，100 IU/kg，每12小时一次；依诺肝素，1 mg/kg，每12小时一次；或0.9%生理盐水，0.25 mL/kg，每6小时一次。每种药物连续给药5天，随后至少有14天的洗脱期。基线和治疗后分析包括抗Xa、TEG以及凝血酶原时间/活化部分凝血活酶时间。
依诺肝素给药4小时后的平均抗Xa活性（0.48 U/mL）接近人类治疗目标（0.5 - 1.0 U/mL）；然而，平均谷值抗Xa活性低于检测限。达肝素给药4小时后的平均抗Xa活性较低，只有1只猫在单个时间点达到治疗目标。接受UFH的猫在谷值和4小时时达到了目标抗Xa活性以及TEG的变化。
在LMWH治疗中，猫具有快速的吸收和消除动力学。基于药代动力学模型，猫需要更高的剂量和更频繁地施用LMWH，以达到0.5 - 1 U/mL的人类治疗性抗Xa活性。预计在施用LMWH后2小时达到抗Xa活性峰值。
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