Alteplase: stability and bioactivity after dilution in normal saline solution.

Area of Science:

• Biochemistry
• Pharmacology
• Biotechnology

Background:

• Alteplase is a crucial thrombolytic agent used in treating various thrombotic events.
• Understanding the stability of reconstituted alteplase under different storage conditions is vital for its effective clinical application.
• Previous studies have focused on refrigerated storage, but data on ambient temperature stability is limited.

Purpose of the Study:

• To evaluate the biochemical stability and bioactivity of alteplase (tissue plasminogen activator) when diluted to 0.01 mg/mL in normal saline.
• To assess the impact of storage at ambient temperature for up to 24 hours on alteplase's properties.
• To determine if commercial saline solution bags maintain the integrity of diluted alteplase.

Main Methods:

• Lyophilized alteplase from 2-mg and 50-mg vials was reconstituted and diluted to 0.01 mg/mL in normal saline.
• Solutions were stored in commercial saline bags at ambient temperature.
• Assays for optical clarity, pH, protein concentration, and in-vitro clot lysis activity were performed at 0, 4, 8, and 24 hours.

Main Results:

• Diluted alteplase solutions maintained optical clarity and remained colorless throughout the 24-hour study period.
• In-vitro clot lysis activity remained largely unchanged, with mean bioactivity of 98.3% (2-mg vial) and 103.1% (50-mg vial) relative to controls.
• Mean protein recovery rates were approximately 42-43% for both vial configurations over 24 hours.

Conclusions:

• Alteplase diluted to 0.01 mg/mL in normal saline is biochemically stable and retains bioactivity for 24 hours at ambient temperature.
• The findings suggest a potential bimodal solubility profile for alteplase in normal saline.
• Further research is recommended to explore the activity and solubility of alteplase at concentrations below 0.01 mg/mL.