METHOD FOR ADMINISTERING AN NMDA RECEPTOR ANTAGONIST TO A SUBJECT
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.
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.