Characterization of alteplase (tPA) following delivery through the AngioJet rheolytic catheter.
OBJECTIVE
To analyze alteplase solutions following delivery through the AngioJet Xpeedior rheolytic thrombectomy device to characterize the viability of proteins exposed to high shear stress.


METHODS
Alteplase solutions were prepared by reconstitution in sterile water to obtain a targeted concentration of 1.0 mg/mL. A baseline control sample was obtained. The AngioJet system was modified by occluding the return line to allow collection of the dispersed fluid volume. Alteplase solutions (n=5) were delivered through the 6-F, 120-cm Xpeedior catheter and collected. All samples were assayed and compared to baseline using qualitative visual inspection, ultraviolet spectrophotometry, size exclusion chromatography, and in vitro clot lysis assays.


RESULTS
Analysis of the test solutions demonstrated a mean protein recovery of 98.0%+/-3.5% of targeted concentration; the collected protein was fully active, as determined by clot lysis assays (specific activity > or =100%). All samples were clear and colorless. No significant fragmentation or aggregation of protein was observed.


CONCLUSIONS
Alteplase solutions, when delivered through the AngioJet Xpeedior rheolytic thrombectomy device, remain stable and biologically active in vitro. Further clinical investigation is warranted using this method as a novel approach for pharmacomechanical thrombolysis.
Semba
Charles P
CP
Division of Vascular Medicine and Neurology, Genentech, Inc., South San Francisco, CA 94080-4990, USA. cpsemba@gene.com
Weck
Suzanne
S
Razavi
Mahmood K
MK
Setum
Cindy M
CM
Patapoff
Thomas
T
D002404:Catheterization / Q000379:methods*; D016503:Drug Delivery Systems; D004867:Equipment Design; D004869:Equipment Safety; D006801:Humans; D066298:In Vitro Techniques; D011673:Pulsatile Flow; D012680:Sensitivity and Specificity; D017131:Thrombectomy / Q000295:instrumentation* / Q000379:methods; D013927:Thrombosis / Q000628:therapy; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D010959:Tissue Plasminogen Activator