Absorption and elimination of a-thrombin and tranexamic acid after fibrin sealant application on resected livers in rabbits

Abstract

Maximum blood concentrations (Cmax) of thrombin and tranexamic acid were evaluated in the bloodstream after local application of a radioactively labelled cryoprecipitate based fibrin (CBF) sealant to a partial liver resection in rabbits. The Cmax of ³H-tranexamic acid reached a peak of 0.015 mg/ml of plasma after 1 h and then slowly cleared within 10 h, never reaching pharmacologically active systemic levels, and demonstrating a slow release from the clot and a fast clearance for the drug. The Cmax of ¹²⁵I-α-thrombin never exceeded 56 milliunits of thrombin equivalent per ml, lower than endogenous thrombin generated in abdominal surgery. Furthermore, the low ratio of trichloroacetic acid precipitable counts versus total counts indicates that the majority of thrombin proteins are in a continuous process of degradation into very small peptides, which are known to be biologically inactive. The bioavailability of tranexamic acid, when embedded in a fibrin sealant, is much longer than when intravenously administered. Conversely, the circulating thrombin resulting from the sealant is low-molecular-weight degradation products with probably no significant biological activity.