Ismail M, Abd-Elsalam M A
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Toxicon. 1988;26(3):233-56. doi: 10.1016/0041-0101(88)90215-2.
The pharmacokinetics of 125I-labelled Androctonus amoreuxi venom and its lethal fraction was studied in rabbits. Comparative pharmacokinetic studies of labelled A. amoreuxi, Leisurus quinquestriatus and Buthotus judaicus venoms were carried out in guinea-pigs. The pharmacokinetics of A. amoreuxi venom was also studied in rats. Groups of rats were injected with labelled A. amoreuxi venom and killed at frequent time intervals for the determination of the relative tissue venom concentration as a function of time. Several groups of rabbits were injected with A. amoreuxi venom and serial blood samples withdrawn at time intervals comparable with those used in the pharmacokinetic studies for the determination of serum glucose, insulin, cortisol, total proteins, albumin, globulins, cholesterol, total bilirubin, urea, uric acid, bicarbonate, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, glucose-6-phosphate dehydrogenase, sodium, potassium, calcium and phosphorus. The packed cell volume, and total and differential leucocyte counts were also determined. In another series of experiments continuous monitoring of the electrocardiograms of rabbits following venom injection was made to correlate any abnormalities with tissue venom concentration. All three venoms and the lethal fraction showed an open two-compartment behaviour with rapid distribution half-lives ranging between 4 and 7 min and overall elimination half-lives of 4.2 to 13.4 hr. The behaviour of A. amoreuxi venom was not markedly different in the three species of animals used. In a given species (guinea-pigs) the behaviour of the three venoms was not markedly different. Correlation of the ECG changes with cardiac venom concentration showed that arrhythmias and infarction occurred at times when cardiac concentration was very low, indicating that the cardiac abnormalities might result from indirect factors. Comparison of the course of the biochemical changes with venom concentration in the central compartment indicated that the site of action of the venom is not located in the central compartment. Correlation of the intensity of the biochemical effects with venom concentration in the peripheral compartment revealed an apparent delay in the onset and peak of action. This was explained by assuming that the tissue compartment could be divided into a rapidly accessible and a slowly accessible compartment with the venom acting through the slowly accessible compartment. There was also the possibility of the venom acting indirectly through the release of other substances or transformation to an intermediate.(ABSTRACT TRUNCATED AT 400 WORDS)
在兔子身上研究了125I标记的以色列金蝎毒液及其致死组分的药代动力学。在豚鼠身上对标记的以色列金蝎、五条纹肥尾蝎和犹大杀牛蝎毒液进行了比较药代动力学研究。还在大鼠身上研究了以色列金蝎毒液的药代动力学。给几组大鼠注射标记的以色列金蝎毒液，并在不同时间间隔处死，以测定相对组织毒液浓度随时间的变化。给几组兔子注射以色列金蝎毒液，并在与药代动力学研究中所用时间间隔相当的时间抽取系列血样，以测定血清葡萄糖、胰岛素、皮质醇、总蛋白、白蛋白、球蛋白、胆固醇、总胆红素、尿素、尿酸、碳酸氢盐、碱性磷酸酶、天冬氨酸转氨酶、乳酸脱氢酶、葡萄糖-6-磷酸脱氢酶、钠、钾、钙和磷。还测定了红细胞压积以及白细胞总数和分类计数。在另一系列实验中，对注射毒液后的兔子心电图进行连续监测，以将任何异常与组织毒液浓度相关联。所有三种毒液及其致死组分均表现出开放的二室行为，分布半衰期迅速，介于4至7分钟之间，总体消除半衰期为4.2至13.4小时。在所使用的三种动物中，以色列金蝎毒液的行为没有明显差异。在给定物种（豚鼠）中，三种毒液的行为也没有明显差异。心电图变化与心脏毒液浓度的相关性表明，心律失常和梗死发生在心脏浓度非常低的时候，这表明心脏异常可能是由间接因素引起的。将生化变化过程与中央室毒液浓度进行比较表明，毒液的作用部位不在中央室。将生化效应强度与外周室毒液浓度进行相关性分析，发现作用的起始和峰值明显延迟。这可以通过假设组织室可分为快速可达和缓慢可达的室，毒液通过缓慢可达的室起作用来解释。毒液也有可能通过释放其他物质或转化为中间体而间接起作用。（摘要截选至400字）
