title: Single-bolus injection of recombinant tissue-type plasminogen activator in acute myocardial infarction.
abstract: Recombinant tissue-type plasminogen activator (rt-PA) has hitherto been administered in acute myocardial infarction as an intravenous infusion with an initial bolus of about 10% of the total dose, both due to its short half-life and to avoid possible early reocclusions. A single-bolus dose would simplify the therapeutic regimen. Therefore, 20 patients with symptom duration of 125 +/- 58 minutes were given a single bolus of 50 mg of rt-PA over 2 minutes. Coronary angiography 60 minutes after the rt-PA bolus revealed a patent infarct-related artery in 15 of 20 patients (patency rate 75%, 95% confidence limits 51 to 91%). In the remaining patients, reperfusion was achieved by coronary angioplasty and intracoronary fibrinolysis; in 2 patients coronary artery bypass grafting was necessary. Control angiograms at 24 hours showed reocclusions in 4 of 18 patients. One woman died due to an intracranial hemorrhage 48 hours after the rt-PA bolus injection. Circulating fibrinogen decreased from 2.7 +/- 0.5 to 1.5 +/- 0.9 g/liter after 2 to 4 hours and reached the initial value within 24 hours. Pharmacokinetic parameters were obtained in 7 patients by measuring rt-PA antigen levels in multiple plasma samples. Mean peak rt-PA concentration was 9.8 +/- 3.6 micrograms/ml, total plasma clearance 476 +/- 148 ml/min and dominant half-life 4.8 +/- 1.0 minutes. Thus, rt-PA administered as a 50-mg single bolus appears to provide similar patency rates and shows similar kinetics in comparison with the conventional infusion regimen. Assessment of the incidence of bleeding complications requires further studies.
authors.affiliation: Department of Cardiology, Georg-August University of Goettingen, Federal Republic of Germany.
authors.forename: U
authors.initials: U
authors.lastname: Tebbe
authors.forename: P
authors.initials: P
authors.lastname: Tanswell
authors.forename: E
authors.initials: E
authors.lastname: Seifried
authors.forename: W
authors.initials: W
authors.lastname: Feuerer
authors.forename: K H
authors.initials: KH
authors.lastname: Scholz
authors.forename: K S
authors.initials: KS
authors.lastname: Herrmann
mesh_terms: D000328:Adult; D000368:Aged; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D003326:Coronary Circulation; D004334:Drug Administration Schedule; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D011994:Recombinant Proteins; D012008:Recurrence; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator