Kurtović Tihana, Karabuva Svjetlana, Grenc Damjan, Dobaja Borak Mojca, Križaj Igor, Lukšić Boris, Halassy Beata, Brvar Miran
Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, Croatia.
Center of Excellence for Virus Immunology and Vaccines, CERVirVac, Rockefellerova 10, 10000 Zagreb, Croatia.
Toxins (Basel). 2021 Apr 14;13(4):279. doi: 10.3390/toxins13040279.
() is the most venomous European viper. The aim of this study was to compare the clinical efficacy and pharmacokinetic values of intravenous venom-specific (paraspecific) Fab fragments (ViperaTAb) and intramuscular venom-specific F(ab') fragments (European viper venom antiserum, also called "Zagreb" antivenom) in -envenomed patients. This was a prospective study of -envenomed patients that were treated intravenously with ViperaTAb or intramuscularly with European viper venom antiserum that was feasible only due to the unique situation of an antivenom shortage. The highest venom concentration, survival, length of hospital stay and adverse reactions did not differ between the groups. Patients treated with intravenous Fab fragments were sicker, with significantly more rhabdomyolysis and neurotoxicity. The kinetics of Fab fragments after one or more intravenous applications matched better with the venom concentration in the early phase of envenomation compared to F(ab') fragments that were given intramuscularly only on admission. F(ab') fragments given intramuscularly had 25-fold longer apparent total body clearance and 14-fold longer elimination half-time compared to Fab fragments given intravenously (2 weeks vs. 24 h, respectively). In -envenomed patients, the intramuscular use of specific F(ab') fragments resulted in a slow rise of antivenom serum concentration that demanded their early administration but without the need for additional doses for complete resolution of all clinical signs of envenomation. Intravenous use of paraspecific Fab fragments resulted in the immediate rise of antivenom serum concentration that enabled their use according to the clinical progress, but multiple doses might be needed for efficient therapy of thrombocytopenia due to venom recurrence, while the progression of rhabdomyolysis and neurotoxic effects of the venom could not be prevented.
（）是欧洲毒性最强的蝰蛇。本研究的目的是比较静脉注射毒液特异性（副特异性）Fab片段（ViperaTAb）和肌肉注射毒液特异性F(ab')片段（欧洲蝰蛇毒抗血清，也称为“萨格勒布”抗蛇毒血清）对中毒患者的临床疗效和药代动力学值。这是一项针对中毒患者的前瞻性研究，这些患者通过静脉注射ViperaTAb或肌肉注射欧洲蝰蛇毒抗血清进行治疗，仅由于抗蛇毒血清短缺的特殊情况才得以实施。两组患者的最高毒液浓度、生存率、住院时间和不良反应并无差异。接受静脉注射Fab片段治疗的患者病情更严重，横纹肌溶解和神经毒性明显更多。与仅在入院时肌肉注射的F(ab')片段相比，一次或多次静脉注射后Fab片段的动力学在中毒早期与毒液浓度的匹配度更好。与静脉注射的Fab片段相比，肌肉注射的F(ab')片段的表观全身清除率长25倍，消除半衰期长14倍（分别为2周和24小时）。在中毒患者中，肌肉注射特异性F(ab')片段导致抗蛇毒血清浓度缓慢上升，这需要早期给药，但无需额外剂量来完全消除中毒的所有临床症状。静脉注射副特异性Fab片段导致抗蛇毒血清浓度立即上升，使其能够根据临床进展使用，但由于毒液复发，可能需要多次剂量才能有效治疗血小板减少症，同时无法预防毒液的横纹肌溶解和神经毒性作用的进展。
