Abstract
Background
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.
Objectives
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.
Results
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.
Conclusion
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.
Keywords
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Article info
Publication history
Accepted:
March 11,
2023
Received in revised form:
February 22,
2023
Received:
November 15,
2022
Publication stage
In Press Accepted ManuscriptIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
