Yap Michelle Khai Khun, Tan Nget Hong, Sim Si Mui, Fung Shin Yee, Tan Choo Hock
CENAR and Department of Molecular Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Basic Clin Pharmacol Toxicol. 2015 Oct;117(4):274-9. doi: 10.1111/bcpt.12398. Epub 2015 Apr 15.
The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.
抗蛇毒血清治疗蛇咬伤的方案在很大程度上仍然是经验性的，部分原因是对蛇毒的药代动力学以及抗蛇毒血清对受害者血液中蛇毒水平的影响了解不足。在本研究中，我们调查了一种多价抗蛇毒血清对实验性中毒兔子体内眼镜蛇（爪哇喷毒眼镜蛇）毒液血清毒液抗原水平的影响。在中毒后1小时静脉输注4毫升神经多价蛇抗毒血清[NPAV，F(ab')2]导致血清毒液抗原水平急剧下降，随后1小时后短暂回升。毒液抗原的回升不太可能是由于F(ab')2与毒液抗原之间药代动力学不匹配，因为F(ab')2在血清中的终末半衰期和分布容积与毒液抗原相当（p>0.05）。再输注2毫升NPAV能够防止血清毒液抗原水平回升，导致在整个中毒过程中循环毒液抗原总量大幅下降（67.1%）。我们结果表明，通过小鼠中和试验确定的NPAV中和效力可能不足以表明其调节毒液动力学的能力与其体内中和毒液毒性效力之间的关系。这些发现还支持在眼镜蛇咬伤时给予高初始剂量NPAV的建议，并在出现抗原血症反弹和症状复发时根据临床情况重复给药。
