Methods of intravenous administration of glyburide
Inventors
Assignees
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Publication Number
US-10391053-B2
Publication Date
2019-08-27
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 disclosed subject matter relates to intravenous glyburide administration, including glyburide for injection referred to as RP-1127, for treating acute ischemic/hemorrhagic stroke, traumatic brain injury (TBI), spinal cord injury (SCI), myocardial infarction (MI), shock, organ ischemia, ventricular arrhythmias, ischemic injury, and hypoxia/ischemia. The disclosure describes achieving therapeutic plasma levels using a bolus followed by continuous infusion for a period of more than 20 hours, including regimens extending to approximately 72 hours.
Multi-phase dosing is used to rapidly reach and maintain therapeutic plasma levels while avoiding excessive levels and hypoglycemia. Phase 1 pharmacokinetic and pharmacodynamic information for RP-1127 is reported, including steady-state Css/Cmax for 0.4 mg/day and 3 mg/day regimens, and discussion of blood glucose monitoring.
The disclosure further describes material compatibility to address concentration loss of glyburide solutions due to adsorption to polyvinyl chloride (PVC). It states that glyburide concentration decreases when in contact with PVC, and therefore recommends PVC-free polyethylene bags/tubing/filters and flushing protocols using a glyburide flushing solution.
Claims Coverage
The partial content includes two independent claims, centered on preventing concentration reduction of glyburide solutions caused by PVC adsorption and on maintaining glyburide concentration within specified limits.
Flushing PVC with a glyburide flushing solution to achieve less than 10% concentration reduction
Contacting a PVC container, tube, and/or filter with a glyburide flushing solution having a glyburide concentration of at least 2 µg/mL, flushing the glyburide flushing solution out, and then refilling with a therapeutic glyburide solution so that a less than 10% reduction in the concentration of the therapeutic glyburide solution is achieved in the PVC container, tube, and/or filter.
Using non-PVC contacting surfaces to limit concentration reduction to no more than 10% with therapeutic glyburide solutions
Providing a PVC container, tube, and/or filter having a surface for contacting the glyburide solution made of a non-PVC material surface, contacting the glyburide therapeutic solution with the non-PVC material surface such that the glyburide solution has a glyburide concentration between 0.5 mg/mL and 1 mg/mL and wherein contacting does not reduce the concentration of the glyburide solution stored in the PVC container, tube, and/or filter by more than 10%.
Across the independent claims, the inventive coverage focuses on controlling glyburide solution concentration loss attributable to PVC contact, either by flushing PVC with a glyburide-containing flushing solution and refilling, or by using non-PVC contacting surfaces so that concentration reduction is limited to the stated less-than-or-equal-to-10% threshold under the defined glyburide concentration range.
Stated Advantages
Achieves a less than 10% reduction in the concentration of the therapeutic glyburide solution in PVC container, tube, and/or filter after flushing and refilling.
Contacting with a non-PVC material surface limits concentration reduction of a glyburide solution stored in a PVC container, tube, and/or filter to no more than 10%.
Avoids excessive glyburide levels and hypoglycemia by using multi-phase dosing to rapidly reach and maintain therapeutic plasma levels.
Documented Applications
Treating acute ischemic/hemorrhagic stroke using intravenous glyburide administration with bolus followed by continuous infusion.
Treating traumatic brain injury (TBI) using intravenous glyburide administration with bolus followed by continuous infusion.
Treating spinal cord injury (SCI) using intravenous glyburide administration with bolus followed by continuous infusion.
Treating myocardial infarction (MI) using intravenous glyburide administration with bolus followed by continuous infusion.
Treating shock using intravenous glyburide administration with bolus followed by continuous infusion.
Treating organ ischemia using intravenous glyburide administration with bolus followed by continuous infusion.
Treating ventricular arrhythmias using intravenous glyburide administration with bolus followed by continuous infusion.
Treating ischemic injury using intravenous glyburide administration with bolus followed by continuous infusion.
Treating hypoxia/ischemia using intravenous glyburide administration with bolus followed by continuous infusion.
Minimizing concentration loss of glyburide solutions due to PVC adsorption by using PVC-related container/tube/filter handling approaches described in the claims.
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