The pharmacokinetics of Iranian scorpion Odonthubuthus doriae venom and the available antivenom.

Journal of Venom Research Pub Date : 2010-10-15
Amir Jalali, Sara Moazen, Mohammad Babaee, Simin Dadashzade, Alireza Droudi
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Abstract

In Iran intramuscular (IM) administration of antivenoms is used for the treatment of human scorpion envenoming of six medically dangerous scorpion species, including Odonthubuthus doriae (O. doriae). The purpose of the current study is to investigate the efficiency of the intramuscular route and the delay of injection on the neutralizing effect of the available polyvalent antivenom. We compared the pharmacokinetics parameters of O. doriae venom and its antivenom. 5µg (131)I-labeled venom and 0.2µl of antivenom were administered via subcutaneous (SC) or IM into rats. Blood samples were taken at various predetermined time intervals during a 24hr period for the venom and a 360min period for the antivenom. The radio-iodination was carried out using the chloramin-T method. The results showed that pharmacokinetic parameters of the venom were T(1/2) = 496.53min; V(d) = 1522ml/kg; Cl = 2.12 ml/kg/min; mean resident residual time (MRT) = 555.77min, and for the antivenom T(1/2) = 902.13min, V(d) = 666.66 ml/kg , Cl = 0.512 ml/kg/min and MRT = 1292min. The total body clearance of the venom is relatively low in agreement with a high mean residence time. Higher AUC and C(max) values for the antivenom as well as its longer residence time indicate that the venom and antivenom are expected to have enough opportunity to interact in the tissue compartments. Over, this study suggests that the intramuscular administration of a single dose of antivenom (2 vials each of 5ml) based on current protocol in Iran is a suitable route for the treatment of envenomation with O. doriae. Prudently, further clinical studies with similar aims need to be carried out to confirm these findings in human victims.

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伊朗蝎毒的药代动力学及现有抗蛇毒血清。
在伊朗,肌内注射抗蛇毒血清用于治疗六种具有医学危险的蝎子(包括多角蝎)的人蝎中毒。本研究的目的是探讨肌内注射途径和注射延迟对现有多价抗蛇毒血清中和作用的影响。比较了桃蚜毒液及其抗蛇毒血清的药动学参数。大鼠皮下注射5µg (131) i标记毒液和0.2µl抗蛇毒血清。在毒液24小时和抗蛇毒血清360分钟的时间间隔内,以不同的预定时间间隔采集血液样本。采用氯胺- t法进行放射性碘化。结果表明,该毒液的药动学参数为T(1/2) = 496.53min;V(d) = 1522ml/kg;Cl = 2.12 ml/kg/min;平均停留时间(MRT) = 555.77min,抗蛇毒血清T(1/2) = 902.13min, V(d) = 666.66 ml/kg, Cl = 0.512 ml/kg/min, MRT = 1292min。毒液的全身清除率相对较低,与较高的平均停留时间一致。抗蛇毒血清较高的AUC和C(max)值以及较长的停留时间表明,预计毒液和抗蛇毒血清有足够的机会在组织区室中相互作用。总之,这项研究表明,根据伊朗目前的方案,肌肉注射单剂量抗蛇毒血清(每5ml 2瓶)是治疗血吸虫中毒的合适途径。需要谨慎地开展具有类似目的的进一步临床研究,以在人类受害者中证实这些发现。
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