Inhibitors of ncca-atp channels for therapy

Abstract

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.