The stability, activity, and compatibility of alteplase with eight drugs frequently used in cardiovascular disease were studied. Alteplase 1 mg/mL was mixed with each of the following: heparin sodium 80 units/mL in 0.9% sodium chloride injection, dobutamine 10 mg/mL (as the hydrochloride salt) in 0.9% sodium chloride injection or 5% dextrose injection, dopamine hydrochloride 1.6 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection, morphine sulfate 2 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection, lidocaine hydrochloride 8 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection, propranolol hydrochloride 1 mg/mL, metoprolol tartrate 1 mg/mL, or nitroglycerin 0.8 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection. Each mixture was assayed immediately and after storage for 24 hours at 25 degrees C; mixtures containing heparin were also assayed at 4 hours. The alteplase concentration and percentage of the single-chain molecule in each mixture were analyzed by using size-exclusion high-performance liquid chromatography (HPLC). Alteplase bioactivity was determined by a clot-lysis assay. Drug concentrations were assayed by HPLC, pH values of the mixtures were determined, and the mixtures were visually inspected. Instability was defined as a > 10% decrease in concentration; inactivity was defined as a > 10% decrease in activity; incompatibility was defined as detection of a precipitate, opalescence, or color change. Alteplase was not stable in the presence of heparin sodium, morphine sulfate, or dobutamine and was not active in the presence of dopamine hydrochloride. Alteplase was compatible with and stable and active (in vitro) in the presence of lidocaine hydrochloride, propranolol hydrochloride, metoprolol tartrate, or nitroglycerin.(ABSTRACT TRUNCATED AT 250 WORDS)