Pharmacokinetics of tissue plasminogen activator in an isolated extracorporeal circuit

Abstract

Purpose: The aim of this study was to investigate the pharmacokinetics of tissue plasminogen activator (tPA) under the conditions of an isolated extracorporeal circuit. Methods: Plasma levels of tPA were measured in the perfusion solution and in central venous blood before, during, and after the perfusion in seven patients undergoing regional hyperthermic fibrinolytic perfusion with tPA in addition to surgical thrombectomy for extended deep venous thrombosis. Results: After 15 minutes of fibrinolytic perfusion, the level of tPA in the perfusion solution was 10,427 ± 4432 ng/mL, and after 30 minutes the maximum level of 19,726 ± 5630 ng/mL was reached. After 60 minutes when the perfusion was discontinued, tPA concentrations dropped to 15,931 ± 4818 ng/mL. In central venous blood, tPA levels increased to a maximum of 230.7 ± 89.6 ng/mL after 60 minutes of perfusion, which represented 1.4% of the concentration measured in the perfusion solution at the same time. With disconnection of the extracorporeal circuit, the tPA levels in central venous blood decreased rapidly and reached a level of 24.1 ± 8.7 ng/mL after 120 minutes. Conclusion: The use of regional hyperthermic fibrinolytic perfusion in the treatment of extended deep venous thrombosis makes it possible to achieve extremely high concentrations of tPA in the perfusion solution. At the same time, the entry of the fibrinolytic agent into the systemic circulation is minimized.