title: A pilot study of the efficacy and safety of bolus administration of alteplase in acute myocardial infarction.
abstract: OBJECTIVE
  To examine the efficacy, safety, and the pharmacokinetic profile of a bolus dose administration regimen of alteplase in the treatment of acute myocardial infarction.
  
  
  METHODS
  An open pilot study.
  
  
  METHODS
  District general hospital.
  
  
  METHODS
  33 suitable consecutive patients presenting within six hours of the onset of symptoms who satisfied the electrocardiographic criteria for acute myocardial infarction.
  
  
  METHODS
  Two intravenous boluses of 35 mg alteplase, 30 minutes apart.
  
  
  METHODS
  Angiographic coronary patency at 90 minutes and 24 hours. Plasma alteplase concentration-time profile and pharmacokinetic analysis.
  
  
  RESULTS
  Coronary patency at 90 minutes: 26 of 30 arteries (87%, 95% confidence interval (CI) 74-99%). Coronary patency at 24 hours: 24 of 29 arteries (83%, CI 69-97%). Mean (SD) plasma tissue plasminogen activator (t-PA) concentration reached 4434.8 (2117.8) and 4233.3 (2217.5) ng/ml within 10 minutes of each bolus and fell to 425.8 (288.3) ng/ml between boluses. The estimated peak concentrations at two minutes after boluses were 12,389 (8580) ng/ml and 10,811 (6802) ng/ml. The derived pharmacokinetic variables were volume of distribution 3.11 (1.89) 1, clearance 21.3 (9.3) 1/h, half life 5.9 (1.7) minutes.
  
  
  CONCLUSIONS
  This simple administration regimen achieved brief, high concentrations of plasma t-PA that were well tolerated. The regimen was associated with a high coronary patency rate at 90 minutes that was well maintained at 24 hours.
authors.affiliation: Department of Medicine and Therapeutics, University of Glasgow, Stobhill General Hospital.
authors.forename: J D
authors.initials: JD
authors.lastname: Gemmill
authors.forename: K J
authors.initials: KJ
authors.lastname: Hogg
authors.forename: P D
authors.initials: PD
authors.lastname: MacIntyre
authors.forename: N
authors.initials: N
authors.lastname: Booth
authors.forename: A P
authors.initials: AP
authors.lastname: Rae
authors.forename: F G
authors.initials: FG
authors.lastname: Dunn
authors.forename: W S
authors.initials: WS
authors.lastname: Hillis
mesh_terms: D000328:Adult; D000368:Aged; D017023:Coronary Angiography; D005069:Evaluation Studies as Topic; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy*; D010865:Pilot Projects; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D010959:Tissue Plasminogen Activator