A 5-Minute Delay From Bolus Injection to Infusion Halves Plasma Concentration of Tissue Plasminogen Activator

Reducing the time between 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 bolus injection; however, only a few studies have investigated the methods and effects of the interrupted time between bolus and post-bolus infusion.

We evaluated the impact of the interrupted time on pharmacokinetic parameters.

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. Post-bolus infusion was initiated at 0-, 5-, 15-, and 30-min intervals after bolus dosing. The calculation interval was set as 6 s.

Alteplase concentration rose to 1.23 mg/mL after 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 post-bolus infusion can cause a significant reduction in serum alteplase concentration.