Pharmacology in Emergency Medicine|Articles in Press

A Five-minute Delay from Bolus Injection to Infusion Halves Plasma Concentration of Tissue Plasminogen Activator



      Reducing the time between the onset of cerebral infarction and treatment with tissue plasminogen activator improves the prognosis of patients with cerebral infarction. Diverse dosing protocols have been developed with the aim of reducing the time to a bolus injection; however, only few studies have investigated the methods and effects of the interrupted time between bolus and postbolus infusion.


      We evaluated the impact of the interrupted time on pharmacokinetics.

      Materials and Methods

      We calculated the changes in alteplase concentration after a bolus injection with high precision, in relation to different interval times. Simulations were performed using the linpk package of the statistical analysis software R. Postbolus infusion was initiated 0, 5, 15, or 30 min intervals after bolus dosing. The calculation interval was set as 6 s.


      Alteplase concentration rose to 1.23 mg/ml following bolus dosing. However, it dropped to 0.53 mg/ml (43.4%) during a 5-min interval, 0.27 mg/ml (22.23%) during a 15-min interval, and 0.10 mg/ml (8.38%) during a 30-min interval.


      Because of the short half-life of alteplase, even a short delay in initiating postbolus infusion can cause a significant reduction in the serum alteplase concentration.


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