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 microg kg(-1) TLE was well fitted by a two-compartment open model. The half-life of the alpha-phase was 18.0+/-3.2 min, and that of the beta-phase 3.9+/-0.7h. The apparent volume of distribution was 1.8+/-0.5l 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(-1) was reached at 5.2+/-0.5h. 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 microg h(-1) ml(-1).