Abstract: This invention is directed towards a ready-to-use aqueous composition of ifosfamide. In one embodiment, the invention is directed to an aqueous ifosfamide composition which comprises ifosfamide, a pharmaceutically acceptable buffer, and water. The concentration of ifosfamide in the composition may be between about 40 mM and about 400 mM. The concentration of buffer in the composition may be between about 10 mM and about 260 mM. The molar ratio of ifosfamide to buffer may be between about 0.5:1 to about 20:1. The pH of the composition may be between about 4 and about 8.

Abstract: The invention includes a packaged liquid composition of a pamidronate alkaline salt in a sealed storage vessel having an inner surface which is non-reactive with the pamidronate alkaline salt composition.

Abstract: This invention is directed towards a ready-to-use aqueous composition of ifosfamide. In one embodiment, the invention is directed to an aqueous ifosfamide composition which comprises ifosfamide, a pharmaceutically acceptable buffer, and water. The concentration of ifosfamide in the composition may be between about 40 mM and about 400 mM. The concentration of buffer in the composition may be between about 10 mM and about 260 mM. The molar ratio of ifosfamide to buffer may be between about 0.5:1 to about 20:1. The pH of the composition may be between about 4 and about 8.

Abstract: Sterile pharmaceutical compositions for parenteral administration containing 2,6-diisopropylphenol (propofol) are described for use as anesthetics. The compositions comprise an oil-in-water emulsion of propofol additionally comprising an amount of sulfite sufficient to prevent significant growth of microorganisms for at least 24 h after adventitious contamination.

Abstract: Sterile pharmaceutical compositions for parenteral administration containing 2,6-diisopropylphenol (propofol) are described for use as anesthetics. The compositions comprise an oil-in-water emulsion of propofol additionally comprising an amount of sulfite sufficient to prevent significant growth of microorganisms for at least 24 h after adventitious contamination.

Abstract: A feedback controlled drug delivery system includes the automated sampling and analysis of a patient sample and dosing the patient based on the analysis. Automated sampling may be performed by direct analysis of the patient sample, such as for the measurement of a blood sample coagulation state or a glucose level. The drug delivery system includes a sample set that has a bidirectional patient tube that allows for delivery of the patient sample to an analyzer, and at another time, the infusion of a therapeutic drug. A controller receives a measurement from the analyzer, and based on that measurement, adjusts the delivery of the therapeutic fluid. The sample set has a quick--clear Leur fitting that allows for more effectively clearing a first fluid from a Leur fitting when starting a second fluid. The system also has a reagent cassette holder that protects, using a foam gasket, a reagent on a sample slide.

Abstract: Methods of preventing tissue damage associated with decreased blood flow in a human by administering AICA riboside or a prodrug thereof in an amount which provides a blood plasma concentration of between 1 .mu.g/ml and 20 .mu.g/ml of AICA riboside for a time sufficient to reduce the risk of said tissue damage in said human. Methods of preventing an adverse clinical outcome, such as an adverse cardiovascular and/or cerebrovascular event, in a patient at risk for such outcome by administering AICA riboside or a prodrug thereof in an amount which provides a blood plasma concentration of between 1 .mu.g/ml and 20 .mu.g/ml of AICA riboside for a time sufficient to reduce the risk for said patient.

Abstract: The present invention relates generally to methods of diagnosis, evaluation and treatment of coronary artery disease in mammals using substituted catecholamines and compounds therefore. It also relates to the preparation, use and administration of these compounds which are useful in the diagnosis, evaluation and treatment of coronary artery disease by means of a feedback controlled drug delivery system that delivers exercise simulating agents which are capable of eliciting acute responses similar to those elicited by aerobic exercise.

Abstract: Analogs of 5-amino-1-beta-D-ribofuranosylimidazole-4-carboxamide (AICA riboside) are provided which are useful in increasing extracellular levels of adenosine.

Abstract: A closed-loop drug delivery system uses patient response and rule based decision making methods to achieve operator specified responses for diagnostic purposes. In the preferred embodiment, cardiac diagnosis is performed by pharmacologically stressing the heart by administration of an exercise simulating agent drug. In the preferred method, a protocol is defined, which preferably includes a target for a physiologic variable, such as heart rate, and a plan to achieve that target value. Preferably, the plan includes a specification of the desired rate of increase in that variable, such as the rate of increase in the heart rate per minute. The plan comprises the desired changes in the physiologic variable as a function of time. While any desired function may be used, the more common modes include RAMP, HOLD, LEVEL and TARGET mode. In one aspect of this invention, the protocol may be varied by the operator after drug administration has begun.

Abstract: Novel diazepine derivatives which selectively inhibit adenosine monophosphate deaminase and methods of preparing these compounds are provided. These compounds are useful in treating certain conditions in vivo which may be ameliorated by increased local concentrations of adenosine.

Abstract: This invention relates to adenosine kinase inhibitors and to nucleoside analogs, specifically to water soluble, aryl substituted 4-amino pyrrolo?2,3-d! pyrimidine and pyrazolo?3,4-d! pyrimidine nucleoside analogs having activity as adenosine kinase inhibitors. The invention also relates to the preparation and use of these adenosine kinase inhibitors in the treatment of cardiovascular, and cerebrovascular diseases, inflammation and other diseases which can be regulated by increasing the local concentration of adenosine.

Abstract: This invention relates to adenosine kinase inhibitors and to nucleoside analogs, specifically to orally active, substituted 5-aryl pyrrolo?2,3-d!pyrimidine and 3-aryl pyrazolo?3,4-d! pyrimidine nucleoside analogs having activity as adenosine kinase inhibitors. The invention also relates to the preparation and use of these and other adenosine kinase inhibitors in the treatment of cardiovascular and cerebrovascular diseases, inflammation and other diseases which can be regulated by increasing the local concentration of adenosine.

Abstract: A feedback controlled drug delivery system includes automated blood sampling and analysis and dosing of the patient. Automated sampling is performed by direct analysis of patient blood, such as for measurement of its coagulation state. A novel manifold includes a fluid input port, a patient port adapted to output fluid and to receive a blood sample from the patient, and a fluid pathway connecting the fluid port and the patient port. A sample line is connected to the fluid pathway to provide the sample to an analyzer. In one aspect of this invention, the sample is forced through the sample line by isolating the patient port, such as by a valve, and non-drug fluid is forced into the manifold causing the blood to cross through the sample line. Alternately, a pump force may be utilized on the sample line. In another aspect of this invention, a positive interlock system is utilized between a drug source and the system.

Abstract: This invention relates to adenosine kinase inhibitors and to nucleoside analogs, C-4' modified pyrrolo?2,3-d!pyrimidine and pyrazolo?3,4-d!pyrimidine nucleoside analogs having activity as adenosine kinase inhibitors. The invention relates to nucleoside analogs of this kind, having zero substitutions or two substitutions at the C-4' position of the furanose (sugar) moiety. The invention also relates to the preparation and use of these adenosine kinase inhibitors in the treatment of cardiovascular, and cerebrovascular diseases, inflammation and other diseases which can be regulated by increasing the local concentration of adenosine.

Abstract: AICA riboside and prodrugs of AICA riboside are provided which lower blood glucose for the treatment of various pathologic conditions, including hypoglycemia, insulin deficiency, insulin resistance diabetes and Syndrome X. Prodrugs of AICA riboside provide AICA riboside in an orally bioavailable form. The use of adenosine kinase inhibition and ZMP enhancement for lowering blood glucose are also described.

Abstract: Novel compounds which selectively inhibit adenosine kinase and methods of preparing adenosine kinase inhibitors are provided. Also provided are methods of treating various inflammatory conditions, including arthritis and SIRS, which may be ameliorated by increased local concentrations of adenosine using adenosine kinase inhibitors.

Abstract: Methods for protecting tissues and organs including the heart central nervous system, and kidney from ischemic damage are described and claimed based upon the recognition that protection against infarction is mediated by A3 rather than A1 adenosine receptors, as was previously thought, and that the receptor mediating protection in other organs and tissues has not been defined. Methods for selectively stimulating A3 adenosine receptors are described and claimed, as such selection is shown to prevent or substantially reduce cell death resulting from ischemia with or without reperfusion in humans. According to this invention, the A3 adenosine receptor is selectively stimulated by administering a compound which is an A3 adenosine receptor-selective agonist. Prevention of tissue death is also achieved by administering a compound which is a non-selective adenosine receptor agonist together with compounds that act as antagonists to the A1 and A2 adenosine receptor.

Abstract: Novel lyxose derivatives which selectively inhibit adenosine kinase and methods of preparing these compounds are provided. These compounds are useful in treating certain conditions in vivo which may be ameliorated by increased local concentrations of adenosine.

Abstract: Methods and devices for the diagnosis, evaluation and treatment of coronary artery disease (CAD) by means of a closed-loop drug delivery system that delivers an exercise simulating agent, including novel exercise simulating agents which elicit both acute and adaptive cardiovascular responses similar to those elicited by aerobic activity are provided. The acute responses to the exercise simulating agent are used to diagnose and evaluate CAD in lieu of the acute responses to aerobic exercise. Due to their adaptive responses these compounds may be used to treat CAD in lieu of the adaptive responses caused by aerobic exercise training or to treat other conditions where the adaptive responses caused by aerobic exercise are desirable.