Method and composition for administering an NMDA receptor antagonist to a subject
View Patent ↗The invention provides methods and compositions for administering an NMDA receptor antagonist (e.g., memantine) to a subject.
1. A method of administering memantine to a human subject in need thereof comprising:
administering to said subject once daily a sustained release oral dosage form comprising 5 to 40 mg of memantine or a pharmaceutically acceptable salt thereof and a component that sustains release of said memantine or salt thereof,
wherein said sustained release memantine provides a change in plasma concentration 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, wherein the dC/dT is measured in a single dose human PK study between the time period of 0 to Tmax of the immediate release form of memantine;
and wherein the subject has a condition selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, and neuropathic pain.
2. The method of claim 1 , wherein the sustained release component comprises a sustained release coating.
3. The method of claim 1 , wherein the dosage form comprises 12.5-40 mg of memantine or salt thereof.
4. The method of claim 1 , wherein the dosage form comprises 25-40 mg of memantine or salt thereof.
5. The method of claim 1 , wherein the dosage form has a memantine in vitro dissolution profile ranging between 0.1-20% in one hour, 5-30% in two hours, 40-80% in six hours, and 50 to 90% in 10 hours, wherein the dissolution profile is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., in 500 ml water.
6. A method of reducing the potential for an adverse effect while administering memantine to a human subject in need thereof, comprising:
orally administering to the human subject once per day a sustained release oral dosage form comprising 5-40 mg of memantine or a pharmaceutically acceptable salt thereof and a component that sustains release of the memantine or salt thereof,
wherein said sustained release memantine provides a change in plasma concentration 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, wherein the dC/dT is measured in a single dose human PK study between the time period of 0 to Tmax of the immediate release form of memantine; and
wherein the subject has a condition selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, and neuropathic pain.
7. The method of claim 6 , wherein the dosage form comprises 12.5 to 40 mg of memantine or salt thereof.
8. The method of claim 6 , wherein the dosage form comprises 25 to 40 mg of memantine or salt thereof.
9. The method of claim 6 , wherein the dosage form has a memantine in vitro dissolution profile ranging between 0.1-20% in one hour, 5-30% in two hours, 40-80% in six hours, and 50 to 90% in 10 hours, wherein the dissolution profile is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., in 500 ml water.
10. A method of administering memantine to a human subject in need thereof comprising:
administering to said subject once daily a sustained release oral dosage form comprising 5 to 40 mg of memantine or a pharmaceutically acceptable salt thereof and a component that sustains release of said memantine or salt thereof,
wherein said sustained release memantine provides a change in plasma concentration as a function of time (dC/dT) in a defined time period of 0 to 6 hours after administration as measured in a single dose human PK study that is less than about 50% of the dC/dT provided by the same quantity of an immediate release form of memantine in said defined time period;
and wherein the subject has a condition selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, and neuropathic pain.
11. The method of claim 10 , wherein the sustained release component comprises a sustained release coating.
12. The method of claim 10 , wherein the dosage form comprises 12.5-40 mg of memantine or salt thereof.
13. The method of claim 10 , wherein the dosage form comprises 25-40 mg of memantine or salt thereof.
14. The method of claim 10 , wherein the dosage form has a memantine in vitro dissolution profile ranging between 0.1-20% in one hour, 5-30% in two hours, 40-80% in six hours, and 50 to 90% in 10 hours, wherein the dissolution profile is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., in 500 ml water.
15. A method of reducing the potential for an adverse effect while administering memantine to a human subject in need thereof, comprising:
orally administering to the human subject once per day a sustained release oral dosage form comprising 5-40 mg of memantine or a pharmaceutically acceptable salt thereof and a component that sustains release of the memantine or salt thereof,
wherein said sustained release memantine provides a change in plasma concentration as a function of time (dC/dT) in a defined time period of 0 to 6 hours after administration as measured in a single dose human PK study that is less than about 50% of the dC/dT provided by the same quantity of an immediate release form of memantine in said defined time period; and
wherein the subject has a condition selected from the group consisting of Alzheimer's disease, dementia, Parkinson's disease, and neuropathic pain.
16. The method of claim 15 , wherein the dosage form comprises 12.5 to 40 mg of memantine or salt thereof.
17. The method of claim 15 , wherein the dosage form comprises 25 to 40 mg of memantine or salt thereof.
18. The method of claim 15 , wherein the dosage form has a memantine in vitro dissolution profile ranging between 0.1-20% in one hour, 5-30% in two hours, 40-80% in six hours, and 50 to 90% in 10 hours, wherein the dissolution profile is determined using a USP type 2 (paddle) dissolution system at 50 rpm, at a temperature of 37±0.5° C., in 500 ml water.