Alteplase as a catheter locking solution: in vitro evaluation of biochemical stability and antimicrobial properties.
OBJECTIVE
To reduce potential complications of fibrin deposition to catheter surfaces, there is increasing empiric use of alteplase as a catheter lock solution. The purpose is to evaluate the properties of alteplase when reconstituted in sterile water (SW) or bacteriostatic water (BW) for prolonged periods.


METHODS
Alteplase in glass vials was reconstituted (1 mg/mL) with SW or BW (0.9% benzyl alcohol) in duplicates and stored at 37 degrees C. Biochemical assays were performed at days 0 and 7 and included optical clarity, protein concentration, percent protein monomer, and in vitro clot lysis activity. Microbiologic assays were performed on days 7 through 28 with use of a standardized antimicrobial effectiveness test (pass/fail) and pour-plate methods incubated at 22.5 degrees C (fungus, 3-7 days) or 32.5 degrees C (bacteria, 3-5 days). Organisms tested included Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger.


RESULTS
Biochemical assay results were as follows: on day 0, all samples were clear/colorless; protein concentrations were 1.10 mg/mL +/- 0 in SW and 1.11 mg/mL +/- 0 in BW; percent protein monomer was 8.2% +/- 0.07 in SW and 98.6% +/- 0.07 in BW; and in vitro clot lysis activity (in percent of relative activity) was 100% in all samples. On day 7, all samples were clear/colorless, protein concentrations were 1.11 mg/mL +/- 0.07 in SW and 1.11 mg/mL +/- 0.07 in BW; percent protein monomer was 97.4% +/- 0.21 in SW and 96.1% +/- 0.21 in BW; and in vitro clot lysis activity (relative activity compared with day 0) was 91% +/- 2.8 in SW and 90% +/- 2.8 in BW. Microbiologic assays (US Pharmacopeia [USP] antimicrobial effectiveness test) yielded a failing result for alteplase reconstituted in SW and a passing result for alteplase reconstituted in BW.


CONCLUSIONS
Alteplase reconstituted with SW or BW remains relatively stable with retained bioactivity when stored at 37 degrees C for as long as 7 days. Despite the biochemical similarities of the two solutions, only alteplase in BW met USP criteria as an effective antimicrobial solution. Further clinical evaluation is warranted.
Weck
Suzanne
S
Department of Pharmaceutical Research and Development, Genetech, South San Francisco, USA.
Cheung
Samantha
S
Hiraoka-Sutow
Martha
M
Patapoff
Thomas
T
Semba
Charles P
CP
D001681:Biological Assay; D002408:Catheters, Indwelling / Q000009:adverse effects; D004355:Drug Stability; D004356:Drug Storage; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D012996:Solutions; D013696:Temperature; D010959:Tissue Plasminogen Activator / Q000737:chemistry*
D012996:Solutions; D010959:Tissue Plasminogen Activator