STABILITY AND ACTIVITY OF ALTEPLASE WITH INJECTABLE DRUGS COMMONLY USED IN CARDIAC THERAPY

The stability, activity, and compatibility of alteplase with eight dru gs frequently used in cardiovascular disease were studied. Alteplase 1 mg/mL was mixed with each of the following: heparin sodium 80 units/m L in 0.9% sodium chloride injection, dobutamine 10 mg/mL (as the hydro chloride salt) in 0.9% sodium chloride injection or 5% dextrose inject ion, dopamine hydrochloride 1.6 mg/mL in 0.9% sodium chloride injectio n or 5% dextrose injection, morphine sulfate 2 mg/mL in 0.9% sodium ch loride injection or 5% dextrose injection, lidocaine hydrochloride 8 m g/mL in 0.9% sodium chloride injection or 5% dextrose injection, propr anolol hydrochloride 1 mg/mL, metoprolol tartrate 1 mg/mL, or nitrogly cerin 0.8 mg/mL in 0.9% sodium chloride injection or 5% dextrose injec tion. Each mixture was assayed immediately and after storage for 24 ho urs at 25 degrees C; mixtures containing heparin were also assayed at 4 hours. The alteplase concentration and percentage of the single-chai n molecule in each mixture were analyzed by using size-exclusion high- performance liquid chromatography (HPLC). Alteplase bioactivity was de termined by a clot-lysis assay. Drug concentrations were assayed by HP LC, pH values of the mixtures were determined, and the mixtures were v isually inspected. Instability was defined as a >10% decrease in conce ntration; inactivity was defined as a >10% decrease in activity; incom patibility was defined as detection of a precipitate, opalescence, or color change. Alteplase was not stable in the presence of heparin sodi um, morphine sulfate, or dobutamine and was not active in the presence of dopamine hydrochloride. Alteplase was compatible with and stable a nd active (in vitro) in the presence of Lidocaine hydrochloride, propr anolol hydrochloride, metoprolol tartrate, or nitroglycerin. Alteplase was compatible with and stable and active in the presence of four of the eight drugs tested.