Pharmacokinetics and systemic fibrinogenolytic effects of recombinant @entity1 tissue-type plasminogen activator (rt-PA) in XXXX .

@entity1 @entity2002 @entity28602
The pharmacokinetics of recombinant @entity1 tissue-type plasminogen activator (rt-PA) were studied in 20 subjects during and after its i.v. infusion at three different rates (5.6, 8.3, and 10 micrograms/kg/min). Steady-state plasma concentrations of 0.9 to 1.6 micrograms/ml were reached. The plasma disappearance curves of rt-PA (both antigen and activity) after cessation of infusion were approximated by a sum of two exponential terms and the turnover of rt-PA was represented by a two-compartment mammillary model with peripheral (liver) elimination. The fractional efflux rate constant from the central compartment was 0.10 per min and the fractional catabolic rate constant about 0.02 per min. After cessation of infusion the initial half-life of the drug in plasma was 6 min. @entity2002 levels were measured by a clotting rate assay and by @entity28602 precipitation. Infusion of rt-PA at 10 micrograms/kg/min for 30 min did not cause systemic @entity2002 breakdown. Infusion of 5.6 micrograms/kg/min for 90 min was associated with a decrease of @entity2002 to 62% of the preinfusion value (4.5 g/l) as measured with the clotting rate assay, but only 2% was recovered as incoagulable @entity2002 -fibrin degradation products. Infusion of 8.3 micrograms/kg/min for 90 min resulted in a decrease of @entity2002 to 45% of the preinfusion level (2.5 g/l) and generation of 8.5% @entity2002 -fibrin degradation products. @entity2002 assays with the @entity28602 method showed a much less extensive decrease of @entity2002 . This extent of systemic fibrinolytic activation and @entity2002 breakdown at high infusion rates and prolonged durations is compatible with that anticipated from the kinetic parameters of the activation of plasminogen by rt-PA.
