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用抗蛇毒血清ViperaTAb治疗极北蝰咬伤:一项药代动力学评估的病例系列研究

Vipera ammodytes bites treated with antivenom ViperaTAb: a case series with pharmacokinetic evaluation.

作者信息

Brvar Miran, Kurtović Tihana, Grenc Damjan, Lang Balija Maja, Križaj Igor, Halassy Beata

机构信息

a Centre for Clinical Toxicology and Pharmacology, University Medical Centre Ljubljana , Ljubljana , Slovenia.

b Faculty of Medicine , Institute of Pathophysiology, University of Ljubljana , Ljubljana , Slovenia.

出版信息

Clin Toxicol (Phila). 2017 Apr;55(4):241-248. doi: 10.1080/15563650.2016.1277235. Epub 2017 Jan 17.

Abstract

CONTEXT

In clinical practice it is difficult to differentiate between V. berus and V. ammodytes venomous bites. In the past this was not a concern, but due to the current shortage in Viperfav™ and European viper venom antiserum availability, V. a. ammodytes venomous bites have recently been treated with ViperaTAb, which is a pharmaceutical formulation containing a monospecific ovine Fab fragments against the venom of V. berus.

OBJECTIVE

To evaluate ViperaTAb in V. a. ammodytes envenomations.

MATERIALS AND METHODS

This is a prospective case series of three consecutive patients envenomed by V. a. ammodytes snakebite treated with ViperaTAb. V. ammodytes venom, neurotoxic ammodytoxins, and Fab fragment levels were determined in serum samples and a pharmacokinetic analysis of the antivenom Fab fragments was carried out.

RESULTS

Three patients bitten by V. a. ammodytes with extensive local swelling, neurological symptoms and recurrent thrombocytopenia were treated with ViperaTAb. V. ammodytes venom was detected in serum of all three patients. Ammodytoxins were detected in the serum of only the most severely envenomed patient who developed neurological symptoms. In the presented moderate cases, a dose of 8 mL of ViperaTAb reduced swelling and improved systemic effects, such as thrombocytopenia. However, this dose of ViperaTAb was not effective in the most severely envenomed patient with the highest serum values of V. ammodytes venom. In this case ViperaTAb did not stop local swelling and it had no effect on neurological signs. ViperaTAb's systemic clearance, distribution and elimination half-lives were 4.3-13.4 mL/h/kg, 1.2-3.2 h and 14.1-55.4 h, respectively.

CONCLUSIONS

In patients envenomed by V. a. ammodytes venom, ViperaTAb reduces moderate swelling and temporarily improves systemic effects, except neurological symptoms. ViperaTAb application induces a decrement of V. ammodytes venom level in the blood, but did not affect serum concentration of neurotoxic ammodytoxins in the one patient with measurable concentrations.

摘要

背景

在临床实践中,很难区分极北蝰(Vipera berus)和角蝰(Vipera ammodytes)的毒蛇咬伤。过去这并非问题,但由于目前抗极北蝰蛇毒血清(Viperfav™)和欧洲蝰蛇毒抗血清供应短缺,最近角蝰的毒蛇咬伤使用了蝰蛇毒抗体(ViperaTAb)进行治疗,这是一种含有针对极北蝰毒液的单特异性羊源Fab片段的药物制剂。

目的

评估蝰蛇毒抗体在角蝰蛇咬伤中毒中的作用。

材料与方法

这是一个前瞻性病例系列,连续纳入3例被角蝰蛇咬伤并接受蝰蛇毒抗体治疗的患者。测定血清样本中的角蝰毒液、神经毒性角蝰毒素和Fab片段水平,并对抗蛇毒血清Fab片段进行药代动力学分析。

结果

3例被角蝰蛇咬伤的患者出现广泛局部肿胀、神经症状和反复血小板减少,接受了蝰蛇毒抗体治疗。所有3例患者的血清中均检测到角蝰毒液。仅在出现神经症状的中毒最严重的患者血清中检测到角蝰毒素。在本研究的中度病例中,8毫升蝰蛇毒抗体剂量减轻了肿胀并改善了全身症状,如血小板减少。然而,该剂量的蝰蛇毒抗体对中毒最严重、血清角蝰毒液值最高的患者无效。在该病例中,蝰蛇毒抗体未能阻止局部肿胀,对神经体征也无影响。蝰蛇毒抗体的全身清除率、分布半衰期和消除半衰期分别为4.3 - 13.4毫升/小时/千克、1.2 - 3.2小时和14.1 - 55.4小时。

结论

在被角蝰毒液中毒的患者中,蝰蛇毒抗体可减轻中度肿胀并暂时改善全身症状,但对神经症状无效。应用蝰蛇毒抗体可使血液中的角蝰毒液水平降低,但在1例可测量浓度的患者中,未影响神经毒性角蝰毒素的血清浓度。

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