EFFECTS OF LIVER BLOOD-FLOW ON THE PHARMACOKINETICS OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR (ALTEPLASE) DURING THROMBOLYSIS IN PATIENTS WITH ACUTE MYOCARDIAL-INFARCTION

Background: The removal of recombinant tissue-type plasminogen activat or (rt-PA; alteplase) by the liver is so rapid that liver blood flow b ecomes rate determining for its clearance, In patients with myocardial infarction changes in liver blood flow may result from impaired cardi ac performance or drug treatment. Objective: To estimate the effect of variations in liver blood now on t-PA plasma concentrations during th rombolytic therapy, Methods: Fifteen patients with acute myocardial in farction were investigated in an open single-center study at the coron ary care unit of University Hospital Leiden, Patients received thrombo lytic treatment with 100 mg rt-PA over 3 hours, Liver blood flow was e stimated by indocyanine green clearance and by Doppler echocardiograph y. Concentrations of t-PA antigen, t-PA activity, indocyanine green, a lpha(2)-antiplasmin, fibrinogen, and fibrin and fibrinogen degradation products were measured. Results: Indocyanine green clearance and clea rance of both t-PA antigen (r = 0.78; p < 0:01) and t-PA activity (r = 0.54; p < 0.05) were significantly related. Significant associations between t-PA antigen and fibrin and fibrinogen degradation products an d between t-PA antigen and alpha(2)-antiplasmin were also found. Concl usions: The liver blood flow of patients with myocardial infarction is inversely correlated with plasma concentrations of t-PA. In patients with severely impaired Liver blood flow and heart failure, high t-PA p lasma concentrations may occur if standard doses are given, This findi ng could contribute to optimization of the dosage of t-PA in certain p atient groups.