Pharmacokinetics of tissue plasminogen activator in an isolated extracorporeal circuit

Purpose: The aim of this study was to investigate the pharmacokinetics of t issue plasminogen activator (tPA) under the conditions of an isolated extra corporeal circuit. Methods: Plasma levels of tPA were measured in the perfusion solution and i n central venous blood before, during, and after the perfusion in seven pat ients undergoing regional hyperthermic fibrinolytic perfusion with tPA in a ddition to surgical thrombectomy for extended deep venous thrombosis. Results: After 15 minutes of fibrinolytic perfusion, the level of tPA in th e perfusion solution was 10,427 +/- 4432 ng/mL, and after 30 minutes the ma ximum 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 di sconnection 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 12 0 minutes. Conclusion: The use of regional hyperthermic fibrinolytic perfusion in the treatment of extended deep venous thrombosis makes it possible to achieve e xtremely high concentrations of tPA in the perfusion solution. At the same time, the entry of the fibrinolytic agent into the systemic circulation is minimized.