INHIBITORS OF NCCA-ATP CHANNELS FOR THERAPY
Methods and compositions are provided that are utilized for treatment and/or prevention of intraventricular hemorrhage or progressive hemorrhagic necrosis (PHN), particularly following spinal cord injury. In particular, the methods and compositions are inhibitors of a particular NC Ca-ATP channel and include, for example, inhibitors of SUR1 and/or inhibitors of TRPM4. Kits for treatment and/or prevention of intraventricular hemorrhage or progressive hemorrhagic necrosis (PHN), particularly following spinal cord injury, are also provided. The present invention also concerns treatment and/or prevention of intraventricular hemorrhage in infants, including premature infants utilizing one or more inhibitors of the channel is provided to the infant, for example to brain cells of the infant.
1 .- 48 . (canceled)
49 . A method of targeting a plasma level of glyburide in an individual, comprising the step of administering glyburide to the individual as follows:
(a) an intravenous loading dose of glyburide; and
(b) a maintenance dose of glyburide, which is different than the loading dose.
50 . The method of claim 49 , wherein the loading dose of glyburide is 30-90 times the amount of the maintenance dose.
51 . The method of claim 50 , wherein the loading dose of glyburide is 40-80 times the amount of the maintenance dose.
52 . The method of claim 50 , wherein the loading dose of glyburide is 50-60 times the amount of the maintenance dose.
53 . The method of claim 49 , wherein the loading dose is 15.7 ug to 665 ug.
54 . The method of claim 53 , wherein the loading dose is 15.7 ug to 117 ug.
55 . The method of claim 49 , wherein the loading dose is 117 ug to 665 ug.
56 . The method of claim 49 , wherein the maintenance dose is 0.3 ug/min to 11.8 ug/min.
57 . The method of claim 56 , wherein the maintenance dose is 0.3 ug/min to 2.1 ug/min.
58 . The method of claim 49 , wherein the total daily dose is 432 ug/day to 17 mg/day.
59 . The method of claim 58 , wherein the total daily dose is 432 ug/day to 3 mg/day.
60 . The method of claim 49 , wherein the targeted plasma level of glyburide is from 4.07 ng/ml to 160.2 ng/ml.
61 . The method of claim 60 , wherein the targeted plasma level of glyburide is from 4.07 ng/ml to 28.3 ng/ml.
62 . The method of claim 49 , wherein the glyburide is administered to said individual for 3 days to 7 days.
63 . The method of claim 62 , wherein the glyburide is administered to said individual for 3 days to 5 days.