A kinetic analysis of fibrinogenolysis during plasminogen activator therapy

A mathematic model of the systemic fibrinogenolysis that accompanies coronary thrombolysis with recombinant tissue plasminogen activator (rt‐PA) has been devised. The kinetic parameters of the model were estimated by nonlinear regression analysis with data from a clinical trial of rt‐PA. The plasma elimination rate constant for rt‐PA was estimated to be 10.0 hr−1, the second‐order catalytic rate constant for the in vivo rt‐PA–mediated conversion of plasminogen to plasmin 0.0078 (μg rt‐PA/kg body weight) −1hr−1, the plasma elimination rate constant for plasmin 2.33 hr−1, and the second‐order catalytic rate constant for the in vivo plasmin‐catalyzed degradation of fibrinogen 0.466 (mg plasmin/dl)−1hr−1. Computer simulation studies based on these parameter estimates show that the magnitude of fibrinogenolysis induced by rt‐PA is related to the dose in a curvilinear fashion, showing diminishing increments in the effect at increasing doses. The degree of fibrinogenolysis induced by rt‐PA administration is nearly independent of the dosing schedule.