Abstract
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 Several groups of rabbits were injected with A. amoreuxi venom and serial blood samples withdrawn at time intervals comparable with those used in the pharmacokinetic studies for the determination of serum glucose, insulin, cortisol, total proteins, albumin,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.