Pharmacokinetics of thrombin-like enzyme from venom of Agkistrodon halys ussuriensis Emelianov determined by ELISA in the rat

A thrombin-like enzyme (TLE) was separated and purified from the venom of a. northeast Chinese snake Agkistrodon halys ussuriensis Emelianov. Experiments were performed in rats to determine the pharmacokinetic parameters following an intravenous (i.v.) or a subcutaneous (s.c.) injection of the thrombin-like enzyme. The plasma levels of TLE were estimated by enzyme-linked immunosorbent assay. The method exhibited high reproducibility and accuracy in correlating optical densities with TLE concentrations (0.2-30 ng ml(-1), r = 0.99). The plasma concentration-time course after i.v. administration of 50 mug kg(-1) TLE was well fitted by a two-compartment open model. The half-life of the a-phase was 18.0 +/- 3.2 min, and that of the beta -phase 3.9 +/- 0.7 h. The apparent volume of distribution was 1.8 +/- 0.5 l kg(-1), and clearance was 5.4 +/- 0.5 ml min(-1) kg(-1). When the TLE was injected s.c. at a dose of 0.75 mg kg(-1), the changes in plasma concentration were best described by a two-compartment model with a first-order absorption. The maximal plasma level of 51 +/- 2.7 ng ml was reached at 5.2 +/- 0.5 h. The absorption rate constant was 0.3 +/- 0.03 h(-1). The area under the plasma concentration-time curve (AUC) was 2.8 +/- 0.8 mug h(-1) ml(-1). (C) 2001 Elsevier Science Ltd. All rights reserved.