Ultrasound-facilitated
catheter-directed thrombolysis is used with low-dose
alteplase to treat
pulmonary embolism. This reduces the risk of
bleeding that accompanies systemic administration of higher
alteplase doses. Some studies suggest that
alteplase given over 2 to 6 hours is safe and effective, but there are few data to support the stability of
alteplase under these conditions. Therefore, we undertook this in vitro study to determine the duration of
alteplase stability.
Alteplase was prepared in solutions of 8 mg in 100 mL, 6 mg in 150 mL, and 8 mg in 200 mL. Solutions were administered through the EkoSonic Endovascular System (with and without ultrasound) to simulate administration over 2, 4, and 6 hours.
Alteplase was assessed with reversed-phase high-performance liquid chromatography (RP-HPLC). Assays were performed at time 0 and at 30-minute intervals during simulated infusion. An
enzyme-linked
immunosorbent assay was used to measure
alteplase concentrations at time 0 and at 15-minute intervals during simulated infusion. By using RP-HPLC in the absence of ultrasound, the
alteplase concentration remained within 1% of the original concentration through 120, 240, and 360 minutes of infusion. By using RP-HPLC for measurement,
alteplase in the presence of ultrasound degraded steadily over time to ∼90% of its original amount in 120 minutes, ∼80% in 240 minutes, and ∼70% in 360 minutes. The remaining
alteplase was available for enzymatic activity.
Alteplase solutions of 0.04 and 0.08 mg/mL degraded steadily over time during simulated ultrasound-facilitated
catheter-directed administration.
Alteplase that did not degrade remained available for enzymatic activity.