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. Experime nts were performed in rats to determine the pharmacokinetic parameters foll owing an intravenous (i.v.) or a subcutaneous (s.c.) injection of the throm bin-like enzyme. The plasma levels of TLE were estimated by enzyme-linked i mmunosorbent 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 h alf-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. T he maximal plasma level of 51 +/- 2.7 ng ml was reached at 5.2 +/- 0.5 h. T he absorption rate constant was 0.3 +/- 0.03 h(-1). The area under the plas ma concentration-time curve (AUC) was 2.8 +/- 0.8 mug h(-1) ml(-1). (C) 200 1 Elsevier Science Ltd. All rights reserved.