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 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 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.

What is claimed is: 
     
         1 . A solid pharmaceutical composition in a unit dosage form for once daily oral administration comprising 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 dC/dT is measured in a single-dose human PK study. 
     
     
         2 . The composition of  claim 1 , comprising 22.5 mg to 30 mg memantine or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The composition of  claim 1 , comprising 28 mg memantine or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The composition of  claim 1 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by 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 dC/dT is measured in a single-dose human PK study. 
     
     
         5 . The composition of  claim 4 , 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. 
     
     
         6 . The composition of  claim 2 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by 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 dC/dT is measured in a single-dose human PK study. 
     
     
         7 . The composition of  claim 6 , 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. 
     
     
         8 . The composition of  claim 3 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by 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 dC/dT is measured in a single-dose human PK study. 
     
     
         9 . The composition of  claim 8 , 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. 
     
     
         10 . A method of treating a patient with a neurological condition selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, and neuropathic pain, comprising once daily orally administering to a human subject in need thereof 22.5 mg to 33.75 mg memantine, or a pharmaceutically acceptable salt thereof, provided in an extended release dosage form, wherein administration of a dose of said dosage form 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 dC/dT is measured in a single-dose human PK study. 
     
     
         11 . The method of  claim 10 , wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia. 
     
     
         12 . The method of  claim 10 , comprising administering 22.5 mg to 30 mg memantine or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of  claim 12 , wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia. 
     
     
         14 . The method of  claim 10 , comprising administering 28 mg memantine or a pharmaceutically acceptable salt thereof. 
     
     
         15 . The method of  claim 14 , wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia. 
     
     
         16 . The method of  claim 10 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by 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 dC/dT is measured in a single-dose human PK study. 
     
     
         17 . The method of  claim 16 , wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia. 
     
     
         18 . The method of  claim 16 , 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. 
     
     
         19 . The method of  claim 18 , wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia. 
     
     
         20 . The method of  claim 12 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by 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 dC/dT is measured in a single-dose human PK study. 
     
     
         21 . The method of  claim 20 , wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia. 
     
     
         22 . The method of  claim 20 , 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. 
     
     
         23 . The method of  claim 22 , wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia. 
     
     
         24 . The method of  claim 14 , wherein administration of a dose of the composition to a human subject provides a mean plasma memantine concentration profile characterized by 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 dC/dT is measured in a single-dose human PK study. 
     
     
         25 . The method of  claim 24 , wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia. 
     
     
         26 . The method of  claim 24 , 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. 
     
     
         27 . The method of  claim 26 , wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia.