Methods of intravenous administration of glyburide
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Publication Number
US-12226521-B2
Publication Date
2025-02-18
Expiration Date
Abstract
The present disclosure is drawn to a method of treating a patient in need of treatment, comprising identifying a patient in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia; administering a bolus of glyburide to the patient; and administering a continuous infusion of glyburide to the patient at from about 15 μg/hr and about 300 μg/hr, wherein the continuous infusion glyburide is administered for a period of time more than about 20 hours.
Core Innovation
The disclosure describes a method of administering glyburide to a subject in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia. The method includes intravenous glyburide treatment using a regimen that begins with a first bolus administration, followed by one or more continuous infusion administrations, to achieve rapid attainment and maintenance of therapeutic glyburide plasma levels while addressing safety concerns associated with excessive exposure and hypoglycemia.
In the described regimen, glyburide is administered over a period of time that includes a first continuous infusion after the first bolus, and then a second continuous infusion after the first continuous infusion. The continuous infusion administrations are carried out at a first rate for a first period of time and then at a second rate for a second period of time, with the rationale for extended multi-hour infusion regimens being maintenance of plasma exposure while avoiding excessive exposure and hypoglycemia.
The disclosure also includes supporting pharmacokinetic/pharmacodynamic findings and handling/formulation considerations affecting glyburide concentration during intravenous administration. The pharmacokinetic/pharmacodynamic characterization includes steady-state concentrations and timing of concentration maxima, and it reports hypoglycemia observations associated with higher dose levels. Additional sections address formulation/device handling to avoid PVC adsorption effects on glyburide concentration, including use of low-sorbing polyethylene-lined containers and filters and associated procedures for maintaining glyburide concentration.
Claims Coverage
The independent claim covers an intravenous glyburide administration method that uses a bolus followed by sequential continuous infusions at different rates and different time periods, for subjects needing treatment for specified ischemic and hypoxia/ischemia-related conditions. The claim includes three main inventive elements: a first bolus administration, a first continuous infusion for a first period at a first rate, and a second continuous infusion for a second period at a second rate.
First bolus administration of glyburide
A method of administering glyburide to a subject includes a first bolus administration of glyburide.
First continuous infusion after the first bolus
A method includes a first continuous infusion administration of glyburide after the first bolus administration, wherein the first continuous infusion glyburide is administered at a first rate of administration for a first period of time.
Second continuous infusion after the first continuous infusion
A method includes a second continuous infusion administration of glyburide after the first continuous infusion of glyburide, wherein the second continuous infusion glyburide is administered at a second rate of administration for a second period of time.
Treatment for specified ischemic and hypoxia/ischemia conditions
The method is used where the subject is in need of treatment for stroke, traumatic brain injury, spinal cord injury, myocardial infarction, shock, organ ischemia, ventricular arrhythmias, ischemic injury, or hypoxia/ischemia.
Overall, the claim coverage is centered on an intravenous glyburide dosing sequence defined by a first bolus followed by two sequential continuous infusions at different administration rates over different time periods, applied to subjects needing treatment for specified stroke/ischemic injury and hypoxia/ischemia-related conditions.
Stated Advantages
Rapid attainment and maintenance of therapeutic glyburide plasma levels.
Avoidance of excessive exposure and hypoglycemia.
Documented Applications
Treatment of stroke, including acute ischemic/hemorrhagic stroke as described in the disclosure.
Treatment of traumatic brain injury.
Treatment of spinal cord injury.
Treatment of myocardial infarction.
Treatment of shock.
Treatment of organ ischemia.
Treatment of ventricular arrhythmias.
Treatment of ischemic injury.
Treatment of hypoxia/ischemia.
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