Method for administering an nmda receptor antagonist to a subject

Abstract

Compositions and methods for administering memantine to a subject are provided. In particular, a solid pharmaceutical composition in a unit dosage form for once daily oral administration is provided. The compositions comprises an extended release formulation of 22.5 mg to 33.75 mg memantine, or a pharmaceutically acceptable salt thereof, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by a change in memantine xconcentration as a function of time (dC/dT) that is less than 50% of the dC/dT provided by the same quantity of an immediate release form of memantine, determined in a time period between 0 hours to 6 hours after administration of memantine, and wherein dC/dT is measured in a single-dose human PK study. Methods of treating dementia, in particular Alzheimer's diseases, using the compositions are provided.

1 .- 27 . (canceled) 
     
     
         28 . A solid pharmaceutical composition in an unit dosage form consisting essentially of 5 to 40 mg memantine or a pharmaceutically acceptable salt thereof provided in an extended release dosage form, wherein administration of the dosage form provides a mean plasma memantine concentration profile characterized by a change in memantine concentration of memantine as a function of time (dC/dT) that is less than about 50% of the dC/dT provided by the same quantity of an immediate release form of memantine, determined in a time period between 0 hours to 6 hours of administration of memantine, and wherein the dC/dT is measured in a single-dose human PK study. 
     
     
         29 . The composition of  claim 28 , consisting essentially of 22.5 mg to 30 mg memantine or a pharmaceutically acceptable salt thereof. 
     
     
         30 . The composition of  claim 28 , consisting essentially of 28 mg memantine or a pharmaceutically acceptable salt thereof. 
     
     
         31 . The composition of  claim 28 , wherein administration of a dose of the composition to a human subject provides a mean plasma meamantine concentration profile characterized by a dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein the dC/dT is measured in a single-dose human PK study. 
     
     
         32 . The composition of  claim 31 , wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine. 
     
     
         33 . The composition of  claim 29 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by a dC/dT that is 2.1 ng/ml/1 hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein the dC/dT is measured in a single-dose human PK study. 
     
     
         34 . The composition of  claim 33 , wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine. 
     
     
         35 . The composition of  claim 30 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by a dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein the dC/dT is measured in a single-dose human PK study. 
     
     
         36 . The composition of  claim 35 , wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine. 
     
     
         37 . A solid pharmaceutical composition in a unit dosage form for once daily oral administration consisting essentially of an extended release formulation of 22.5 mg to 33.75 mg memantine, or a pharmaceutically acceptable salt thereof, wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by a change in memantine concentration as a function of time (dC/dT) that is less than 50% of the dC/dT provided by the same quantity of an immediate release form of memantine, determined in a time period between 0 hours to 6 hours after administration of memantine, and wherein the dC/dT is measured in a single-dose human PK study. 
     
     
         38 . The composition of  claim 37 , consisting essentially of 22.5 mg to 30 mg memantine or a pharmaceutically acceptable salt thereof. 
     
     
         39 . The composition of  claim 37 , consisting essentially of 28 mg memantine or a pharmaceutically acceptable salt thereof. 
     
     
         40 . The composition of  claim 37 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by a dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein the dC/dT is measured in a single-dose human PK study. 
     
     
         41 . The composition of  claim 40 , wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine. 
     
     
         42 . The composition of  claim 38 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by a dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein before the dC/dT is measured in a single-dose human PK study. 
     
     
         43 . The composition of  claim 42 , wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine. 
     
     
         44 . The composition of  claim 39 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by a dC/dT that is 2.1 ng/ml/hr or less, determined in a time period of 0 hours to 4 hours after administration of memantine, and wherein before the dC/dT is measured in a single-dose human PK study. 
     
     
         45 . The composition of  claim 44 , wherein the dC/dT of 2.1 ng/ml/hr or less is determined in a time period of 2 hours to 4 hours after administration of memantine.