Pharmacokinetics of Tityus serrulatus scorpion venom determined by enzyme-linked immunosorbent assay in the rat
1996
Santana, G.C. | Freire, A.C.T. | Ferreira, A.P.L. | Chaves-Olortegui, C. | Diniz, C.R. | Freire-Maia, L.
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 micrograms/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 micrograms/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 micrograms/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 (t1/2 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 (t1/2 beta = 173.25 min).
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