Pharmacokinetics of human recombinant tissue-type plasminogen activator, administered intra-abdominally, in a rat peritonitis model

Abstract

Human recombinant tissue-type plasminogen activator (rtPA), administered intraperitoneally, may promote intra-abdominal fibrinolysis in peritonitis, thereby preventing adhesion and abscess formation. The pharmacokinetics of a single intraperitoneal dose of 0.5 or 2.0 mg/ml human rtPA were assessed in rats with fecal peritonitis and related to their endogenous tPA and plasminogen activator inhibitor (PAI) activity. Endogenous PAI activity was strongly elevated both in peritoneal fluid and in plasma, whereas tPA activity was only slightly increased in the peritoneal fluid. Both doses of rtPA significantly enhanced fibrinolytic activity of the peritoneal fluid up to 24 h in a dose-dependent manner. However, tPA activity was lower than calculated from the tPA antigen levels and the specific activity of rtPA in the fluid of rats with peritonitis. Plasma tPA activity was low at both doses. A single dose of 0.5 or 2.0 mg/ml rtPA can raise fibrinolytic activity in the abdominal cavity up to 24 h. High endogenous peritoneal PAI levels may adversely effect intra-abdominal use of human rtPA in peritonitis.