title: Clinical pharmacology in patients with evolving myocardial infarction of tissue-type plasminogen activator produced by recombinant DNA technology.
abstract: This study was performed to characterize selected pharmacologic properties and effects on the fibrinolytic system of tissue-type plasminogen activator synthesized by recombinant DNA technology (rt-PA) in 12 patients treated for coronary thrombosis. rt-PA was infused parenterally (by the intracoronary route in four patients and intravenously in eight) in doses of 8.3, 12.5, or 16.7 micrograms/kg/min for 30 to 60 min, yielding a total dosage of 20 to 40 mg/patient. The drug induced coronary thrombolysis in 10 of the 12 patients treated (83%), including six of the eight given rt-PA intravenously. No bleeding complications were encountered. Serial blood samples were obtained before, during, and after infusion of rt-PA and analyzed for t-PA antigen (i.e., immunoassayable rt-PA protein), functional fibrinolytic activity attributable to rt-PA, fibrinogen, plasminogen, alpha 2-antiplasmin, fibrinogen degradation products, prothrombin time, activated partial thromboplastin time, and protamine-corrected thrombin time. Pretreatment plasma t-PA antigen levels averaged 16.5 +/- 5(SD) ng/ml. Peak plasma values were generally proportional to dose, averaging 3330 +/- 1201 ng/ml. Approximately 90% of peak level was reached in 30 min, with a plateau at peak reached within 40 min. Functional t-PA activity increased monotonically in a comparable fashion. Curves for disappearance of both t-PA antigen and functional activity from plasma were monoexponential for at least two half-lives (r = .99 for both) and were concordant. The observed half-lives were similar, averaging 8.3 and 9.1 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D004274:DNA, Recombinant; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000097:blood*; D011863:Radioimmunoassay; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D004274:DNA, Recombinant; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D010958:Plasminogen; D010960:Plasminogen Activators