Methods for the treatment of a traumatic central nervous system injury

Abstract

Methods of treating a subject with a traumatic central nervous system injury, more particularly, a traumatic brain injury, are provided. The methods comprise a therapy comprising a constant or a two-level dosing regime of progesterone. In one method, a subject in need thereof is administered at least one cycle of therapy, wherein the cycle of therapy comprises administering a therapeutically effective two-level intravenous dosing regime of progesterone. The two-level dosing regime comprises a first time period, wherein a higher hourly dose of progesterone is administered to the subject, followed by a second time period, wherein a lower hourly dose of progesterone is administered to the subject.

1 . A method of treating a traumatic brain injury in a human subject, said method comprising administering to said subject in need thereof at least one cycle of therapy, wherein said cycle of therapy comprises administering a therapeutically effective two-level intravenous dosing regime of progesterone, said two-level dosing regime comprising a first time period, wherein a higher hourly infusion dose of progesterone is administered to the subject, followed by a second time period, wherein a lower hourly infusion dose of progesterone is administered to said subject. 
   
   
       2 . The method of  claim 1 , wherein the first time period comprises an infusion dose of progesterone of about 0.1 mg/kg/hr to about 7.1 mg/kg/hr. 
   
   
       3 . The method of  claim 2 , wherein the first time period comprises an infusion dose of progesterone of about 0.71 mg/kg/hr. 
   
   
       4 . The method of  claim 1 , wherein the second time period comprises an infusion dose of progesterone of about 0.05 mg/kg/hr to about 5 mg/kg/hr. 
   
   
       5 . The method of  claim 4 , wherein the second time period comprises an infusion dose of about 0.5 mg/kg/hr. 
   
   
       6 . The method of  claim 1 , wherein the second time period comprises about a 24 hour to about a 120 hour period. 
   
   
       7 . The method of  claim 6 , wherein the second time period comprises about a 71 hour period. 
   
   
       8 . The method of  claim 1 , wherein the first time period comprises an infusion dose of progesterone of about 0.71 mg/kg/hr, the second time period comprises an infusion dose of about 0.5 mg/kg/hr, the first time period comprises about 1 hour, and the second time period comprises about a 71 hour period. 
   
   
       9 . The method of  claim 1 , wherein the two-level intravenous dosing regime of progesterone results in a progesterone serum level in said subject of about 100 ng/ml to about 2000 ng/ml. 
   
   
       10 . The method of  claim 9 , wherein the progesterone serum level is about 350 ng/ml to about 450 ng/ml. 
   
   
       11 . The method of  claim 1 , further comprising a third time period, wherein said third time period comprises a tapered administration of the progesterone to the subject. 
   
   
       12 . The method of  claim 1 , wherein the first and the second time periods are continuous. 
   
   
       13 . The method of  claim 1 , wherein the first and the second time periods are discontinuous. 
   
   
       14 . The method of  claim 1 , wherein said first time period comprises a bolus injection.