Compositions for the treatment of cns-related conditions

Abstract

The invention provides methods for treating CNS-related conditions with amantadine and donepezil, in which the amantadine is in an extended release form, wherein the extended release amantadine formulation provides a change in plasma concentration as a function of time (dC/dT) that is less than 40% of the dC/dT of the same quantity of an immediate release form of amantadine.

1 - 10 . (canceled) 
     
     
         11 . A solid pharmaceutical composition in a unit dosage form for once daily, oral administration comprising:
 a) a first drug selected from the group consisting of memantine and a pharmaceutically acceptable salt thereof in an amount of 22.5 mg to 33.75 mg;   b) a second drug selected from the group consisting of donepezil and a pharmaceutically acceptable salt thereof in an amount of 1 mg to 10 mg; and   c) at least one excipient that modifies release of said first drug to provide an extended release form of said first drug,   wherein oral administration of a dose of said pharmaceutical composition to a human subject of a fasted single dose human pharmacokinetic study provides a plasma concentration profile of memantine characterized by a change in plasma concentration of memantine as a function of time (dC/dT) that is less than about 50% of a change in plasma concentration of memantine as a function of time (dC/dT) determined for oral administration of an equal dose of said first drug in an immediate release form to a human subject of a fasted single dose human pharmacokinetic study,   wherein the dC/dT for both said pharmaceutical composition and said immediate release form of said first drug are determined in a time period between 0 hours and 6 hours of administration of said pharmaceutical composition and said immediate release form to a human subject in the same concurrent fasted single dose human pharmacokinetic study.   
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein the amount of the first drug in the pharmaceutical composition is 25 mg to 30 mg. 
     
     
         13 . The pharmaceutical composition of  claim 12 , wherein the amount of the second drug in the pharmaceutical composition is 5 mg to 10 mg. 
     
     
         14 . The pharmaceutical composition of  claim 11 , wherein the amount of the second drug in the pharmaceutical composition is 5 mg to 10 mg. 
     
     
         15 . (canceled) 
     
     
         16 . (canceled) 
     
     
         17 . The pharmaceutical composition of  claim 11 , wherein said pharmaceutical composition provides a change in plasma concentration of memantine as a function of time of 2.1 ng/ml/hr or less in a human subject of a fasted single dose human pharmacokinetic study determined in a time period between 0 hours and 4 hours after administration of said pharmaceutical composition to said subject of a fasted single dose human pharmacokinetic study. 
     
     
         18 . The pharmaceutical composition of  claim 11 , wherein said pharmaceutical composition provides a change in plasma concentration of memantine as a function of time of 2.1 ng/ml/hr or less in a human subject of a fasted single dose human pharmacokinetic study determined in a time period between 2 hours and 4 hours after administration of said pharmaceutical composition to said subject of a fasted single dose human pharmacokinetic study. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The pharmaceutical composition of  claim 11 , wherein the amount of the first drug in the pharmaceutical composition is 28 mg. 
     
     
         22 . The pharmaceutical composition of  claim 11 , wherein the first drug is memantine hydrochloride. 
     
     
         23 . (canceled) 
     
     
         24 . The pharmaceutical composition of  claim 11 , wherein oral administration of a dose of said pharmaceutical composition provides a change in mean plasma concentration of memantine as a function of time that is less than about 50% of a change in mean plasma concentration as a function of time determined for oral administration of an equal dose of an immediate release form of said first drug,
 wherein the change in mean plasma concentration of memantine for said pharmaceutical composition and said immediate release form of said first drug are both determined in a time period between 0 hours and 6 hours of administration of said pharmaceutical composition and said immediate release form of said first drug to human subjects in the same concurrent fasted single dose human pharmacokinetic study.   
     
     
         25 . A solid pharmaceutical composition in a unit dosage form for once daily, oral administration comprising:
 a) a first drug selected from the group consisting of memantine and a pharmaceutically acceptable salt thereof in an amount of 22.5 mg to 33.75 mg;   b) a second drug selected from the group consisting of donepezil and a pharmaceutically acceptable salt thereof in an amount of 1 mg to 10 mg; and   c) at least one excipient that modifies release of said first drug to provide an extended release form of said first drug,   wherein oral administration of a dose of said pharmaceutical composition to a human subject of a fasted single dose human pharmacokinetic study provides a plasma concentration profile of memantine characterized by a change in plasma concentration of memantine as a function of time (dC/dT) per mg of said first drug that is less than about 50% of a change in plasma concentration of memantine as a function of time (dC/dT) per mg of said first drug determined for oral administration of an immediate release form of said first drug to a human subject of a fasted single dose human pharmacokinetic study,   wherein the dC/dT per mg for both said pharmaceutical composition and said immediate release form of said first drug are determined in a time period between 0 hour to 6 hours of administration of said pharmaceutical composition and said immediate release form to a human subject in the same concurrent fasted single dose human pharmacokinetic study.   
     
     
         26 . The pharmaceutical composition of  claim 25 , wherein the amount of said first drug in the pharmaceutical composition is 25 mg to 30 mg. 
     
     
         27 . The pharmaceutical composition of  claim 26 , wherein the amount of said second drug in the pharmaceutical composition is 5 mg to 10 mg. 
     
     
         28 . The pharmaceutical composition of  claim 25 , wherein the amount of the second drug in the pharmaceutical composition is 5 mg to 10 mg. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . The pharmaceutical composition of  claim 25 , wherein said pharmaceutical composition provides a change in plasma concentration of memantine as a function of time of 2.1 ng/ml/hr or less in a human subject of a fasted single dose human pharmacokinetic study determined in a time period between 0 hours and 4 hours after administration of said pharmaceutical composition to said subject of a fasted single dose human pharmacokinetic study. 
     
     
         32 . The pharmaceutical composition of  claim 25 , wherein said pharmaceutical composition provides a change in plasma concentration of memantine as a function of time of 2.1 ng/ml/hr or less in a human subject of a fasted single dose human pharmacokinetic study determined in a time period between 2 hours and 4 hours after administration of said pharmaceutical composition to said subject of a fasted single dose human pharmacokinetic study. 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . The pharmaceutical composition of  claim 25 , wherein the amount of the first drug in the pharmaceutical composition is 28 mg. 
     
     
         36 . The pharmaceutical composition of  claim 25 , wherein the first drug is memantine hydrochloride. 
     
     
         37 . (canceled) 
     
     
         38 . The pharmaceutical composition of  claim 25 , wherein oral administration of a dose of said pharmaceutical composition provides a change in mean plasma concentration of memantine as a function of time per mg of said first drug that is less than about 50% of a change in mean plasma concentration as a function of time per mg of said first drug determined for oral administration of an immediate release form of said first drug,
 wherein the change in mean plasma concentration of memantine for said pharmaceutical composition and said immediate release form of said first drug are both determined in a time period between 0 hours and 6 hours of administration of said pharmaceutical composition and said immediate release form of said first drug to human subjects in the same concurrent fasted single dose human pharmacokinetic study.