Kinetics of transperitoneal tissue-type plasminogen activator absorption

Peritoneal hypofibrinolysis has been suggested to be a central denominator in the formation of postoperative adhesions. Topical application of tissue-type plasminogen activator (t-PA) has been demonstrated to reduce adhesion formation, but the absorption of t-PA is not known. The aim of the present study was to determine the absorptive kinetics of t-PA by injecting varying doses of t-PA in intraperitoneally (i.p.) in rats. Plasma elimination was investigated in another set of experiments, where the same doses were injected intravenously (i.v.), The concentrations of t-PA in plasma were dose-dependent after both administrations, and at three and six hours the t-PA concentration in plasma was significantly higher after i.p. [64 (12.8) ng/mL (40 mu g dose)] and [297.6 (6.7) (400 mu g dose)] then after i.v. [27.9 (15.8) (40 mu g dose)] and [127.0 (35.0) (400 mu g dose)] (P<0.05). Uptake rate of t-PA from the peritoneal cavity was 2.4-6.2 mu L/min, which is compatible with peritoneal lymph flow, Plasma clearance was rapid after an i.v. injection (3.3-5.7 mL/min), and slower (0.8-1.7 mL/min) after i.p. administration, indicating a greater availability of t-PA when given i.p. To increase abdominal fibrinolytic capacity without affecting systemic fibrinolysis, a slow-release form of t-PA has to be used. The finding that i.p. administration gave rise to prolonged elevation of plasma concentration as compared to an i.v. injection may have some therapeutic implications in thrombolysis.