Pharmacokinetics and haemostatic status during consecutive infusions of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction.
Pharmacokinetics and systemic effects of recombinant tissue-type plasminogen activator (rt-PA) were determined during coronary thrombolysis in 12 acute myocardial infarction patients using a consecutive intravenous infusion regimen. Ten mg rt-PA were infused in 2 minutes resulting in a peak plasma concentration (mean +/- SD) of 3310 +/- 950 ng/ml, followed by 50 mg in 1 h and 30 mg in 1.5 h yielding steady state plasma levels of 2210 +/- 470 ng/ml and 930 +/- 200 ng/ml, respectively. All patients received intravenous heparin. Total clearance of rt-PA was 380 +/- 74 ml/min, t1/2 alpha was 3.6 +/- 0.9 min and t1/2 beta was 16 +/- 5.4 min. After 90 min, in plasma samples containing anti-rt-PA-IgG to inhibit in vitro effects, fibrinogen was decreased to 54%, plasminogen to 52%, alpha 2-antiplasmin to 25%, alpha 2-macroglobulin to 90% and antithrombin III to 85% of initial values. Coagulation times were prolonged and fibrin D-dimer concentrations increased from 0.40 to 2.7 micrograms/ml. It is concluded that pharmacokinetics of rt-PA show low interpatient variability and that its short mean residence time in plasma allows precise control of therapy. Apart from its moderate effect on the haemostatic system, rt-PA appears to lyse a fibrin pool in addition to the coronary thrombus.
Seifried
E
E
Abteilungen III, Universität Ulm, FRG.
Tanswell
P
P
Ellbrück
D
D
Haerer
W
W
Schmidt
A
A
D000368:Aged; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000493:pharmacokinetics*
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator