ABSTRACT
The stability and compatibility of tirofiban hydrochloride injection during simulated Y-site administration with various other drugs were studied. Tirofiban hydrochloride, dobutamine, epinephrine hydrochloride, furosemide, midazolam hydrochloride, and propranolol hydrochloride injections were each prepared from their respective concentrates in both 0.9% sodium chloride injection and 5% dextrose injection at both the minimum and maximum concentrations normally administered. The high-concentration solutions of midazolam hydrochloride and furosemide were used as is. Morphine sulfate was diluted in 5% dextrose injection only. Nitroglycerin premixed infusions, atropine sulfate injection, and diazepam injection were used as is. Tirofiban hydrochloride solutions were combined 1:1 with each of the secondary drug solutions in separate glass containers. Samples were stored for four hours at room temperature under ambient fluorescent light and were assayed for drug content and degradation by high-performance liquid chromatography and for pH, appearance, and turbidity. All mixtures except those containing diazepam remained clear and colorless, with no visual or turbidimetric indication of physical instability. Mixing of tirofiban hydrochloride and diazepam solutions resulted in immediate precipitation. all remaining mixtures remained clear. There was no significant loss of any of the drugs tested, no increase in known degradation products, and no appearance of unknown drug-related peaks. The pH of all test solutions remained constant. Tirofiban hydrochloride injection 0.05 mg/mL was stable for at least four hours when combined 1:1 in glass containers with atropine sulfate, dobutamine, epinephrine hydrochloride, furosemide, midazolam hydrochloride, morphine sulfate, nitroglycerin, and propranolol hydrochloride at the concentrations studied. Tirofiban hydrochloride was incompatible with diazepam.
Subject(s)
Chemistry, Pharmaceutical , Platelet Aggregation Inhibitors/administration & dosage , Tyrosine/analogs & derivatives , Tyrosine/administration & dosage , Chromatography, High Pressure Liquid , Drug Combinations , Drug Stability , Drug Storage , Solutions , TirofibanABSTRACT
OBJECTIVE: To study the compatibility of tirofiban HCl injection 0-05 mg/ml with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride infusion solutions during simulated Y-site administration. METHOD: Tirofiban HCl, dopamine HCl, famotidine, lidocaine HCl and potassium chloride infusions were each prepared from their respective concentrates as per current clinical preparation instructions in both 0.9% sodium chloride and 5% dextrose solutions at both the minimum and maximum concentrations normally administered. Sodium heparin premixed infusion solutions in 5% dextrose and 0-45% sodium chloride were used as-is. Tirofiban HCl solutions were combined 1:1 (simulated Y-site administration) with the dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride solutions in separate glass containers and polyvinylchloride Y-site infusion lines. Samples were held for 4 h at room temperature under ambient fluorescent light and were assayed for changes in drug content, degradation, pH, appearance and turbidity. Activity of sodium heparin solutions was measured using an aPTT coagulation assay. RESULTS: All mixtures remained clear and colourless with no visual indication of instability, i.e. precipitation. Clarity of solutions was confirmed by turbidometric analysis. There was no significant loss of drug, increase in known degradates, or appearance of unknown drug-related peaks as determined by HPLC. The activity of heparin in heparin-containing solutions remained unchanged. The pH of all test-solutions remained constant. CONCLUSION: Tirofiban HCl injection 0.05 mg/ml can be co-infused by Y-site administration with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride injection solutions.
Subject(s)
Platelet Aggregation Inhibitors/chemistry , Tyrosine/analogs & derivatives , Chromatography, High Pressure Liquid , Dopamine/administration & dosage , Dopamine/chemistry , Drug Incompatibility , Drug Stability , Famotidine/administration & dosage , Famotidine/chemistry , Heparin/administration & dosage , Heparin/pharmacology , Hydrogen-Ion Concentration , Injections, Intravenous , Lidocaine/administration & dosage , Lidocaine/chemistry , Platelet Aggregation Inhibitors/administration & dosage , Potassium Chloride/administration & dosage , Potassium Chloride/chemistry , Time Factors , Tirofiban , Tyrosine/administration & dosage , Tyrosine/chemistryABSTRACT
In a randomized, two-period crossover study in 12 normal volunteers, serum and urine concentrations of the angiotensin-converting enzyme inhibitor enalapril and its active metabolite enalaprilat were determined following administration of a single 40-mg tablet of enalapril maleate administered both in the fasting state and with a standard breakfast. A 7-d interval separated the two treatment periods. Area under the serum concentration-time curves for enalaprilat and urinary recoveries for enalaprilat and total drug did not differ significantly between the fed and fasted conditions. The mean observed maximum serum concentration of enalaprilat was slightly higher for the fasting treatment, but the time to peak concentration was almost identical for the two treatments. Enalapril maleate is unlike the prototype angiotensin-converting enzyme inhibitor captopril in that a standard meal does not appear to influence absorption of this new drug.
