Comparison of pharmacokinetics of lanoteplase and alteplase during acute myocardial infarction

J. B. Kostis, R. C. Dockens, U. Thadani, V. Bethala, C. Pepine, W. Leimbach, N. Vachharajani, R. H. Raymond, B. C. Stouffer, L. K. Tay, W. C. Shyu, W. C. Liao

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12 Scopus citations


Objective: Lanoteplase is a rationally designed variant of tissue plasminogen activator. The aim of this study was to examine the pharmacokinetics and functional activity of a single intravenous bolus dose of lanoteplase with those of a bolus plus two-step infusion of alteplase. Design: Seven-centre substudy of the InTIME-I angiographic trial in patients presenting within 6 hours of onset of suspected acute myocardial infarction. Patients and Participants: A total of 31 patients (28 males, 3 females) enrolled in this substudy [mean age 59 (range 26 to 76) years]. Methods: Twenty-three patients randomised to lanoteplase received single bolus doses of 15 kU/kg (n = 5), 30 kU/kg (n = 3), 60 kU/kg (n = 9), or 120 kU/kg (n = 6). Eight patients received alteplase ≤100mg as a bolus followed by a two-stage 90 min infusion. Blood samples were analysed for antigen concentration and plasminogen activator (PA) activity. Results: The distribution plasma half-life of approximately 35 min for lanoteplase was at least five times longer than that of alteplase. Lanoteplase plasma clearance averaged 3 L/h (50 ml/min), whereas the mean plasma clearance of approximately 24 L/h (400 ml/min) for alteplase approaches hepatic blood flow following acute myocardial infarction. PA activity after lanoteplase 120 kU/kg remained for 6 hours, compared with less than 4 hours after alteplase 100mg. Conclusions: The longer antigen and activity half-lives, slower clearance and less complicated administration of lanoteplase compared with alteplase suggest that it may offer advantages for use as a single intravenous bolus to achieve reperfusion after myocardial infarction.

Original languageEnglish (US)
Pages (from-to)445-452
Number of pages8
JournalClinical Pharmacokinetics
Issue number6
StatePublished - 2002

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)


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