PHARMACOKINETICS OF TITYUS SERRULATUS SCORPION VENOM DETERMINED BY ENZYME-LINKED IMMUNOSORBENT ASSAY IN THE RAT

摘要

Experiments were performed in two groups of anaesthetized rats to study the genesis of pulmonary oedema and to determine the pharmacokinetic parameters following a subcutaneous (s.c.) injection of Tityus serrulatus scorpion venom. In group 1, the rats were anaesthetized with pentobarbital (4 mg/100 g, i.p.); the s.c. injection of scorpion venom at the dose of 50 mu g/100 g did not induce arterial hypertension, but unilateral pulmonary oedema was observed in three of six rats. The injection of a higher dose of venom (200 mu g/100 g, N = 6) induced arterial hypertension and bilateral (N = 3) or unilateral (N = 1) pulmonary oedema. These data indicate that it is possible to evoke unilateral pulmonary oedema without previous arterial hypertension induced by the venom. For the study of pharmacokinetic parameters a second group of six rats was anaesthetized with urethane (140 mg/100 g, i.p.) and the venom injected at a dose of 200 mu g/100 g, s.c. The plasma concentrations of venom were determined by enzyme-linked immunosorbent assay, at times 0, 5, 30, 60, 180, 360, and 720 min after venom injection. A biphasic curve was obtained with an ascending phase followed by a descending phase. The maximum plasma scorpion venom concentration was reached at 60 min. The pharmacokinetic parameters showed a fast absorption rate (K-a = 0.058 min(-1)), a fast and high distribution of venom to tissues (t(1/2)alpha = 31.50 min and V-d area = 6800.47 ml.kg(-1), respectively), a great affinity of the venom for the tissues (K-CT = 0.056 min(-1) and K-TC = 0.002 min(-1)) and a slow elimination half-life (t(1/2)beta = 173.25 min). Copyright (C) 1996 Elsevier Science Ltd [References: 13]