Compositions for the treatment of cns-related conditions

A method of treating a human subject for a neurological condition, comprising orally administering once a day to said human subject a pharmaceutical composition in a unit dosage form 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 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 an immediate release form of said first drug to a human subject of said 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 hour to 6 hours of administration of said pharmaceutical composition and said immediate release form of said first drug to a human subject in the same single dose human pharmacokinetic study;
• and
• wherein said neurological condition is selected from the group consisting of Alzheimer's disease and dementia.

A method of treating a human subject for a neurological condition, comprising orally administering once a day to said human subject a pharmaceutical composition in a unit dosage form 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 the 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 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 said 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 hours to 6 hours of administration of said pharmaceutical composition and said immediate release form of said first drug to a human subject in the same single dose human pharmacokinetic study;
• and
• wherein said neurological condition is selected from the group consisting of Alzheimer's disease and dementia.

A method of reducing a potential for an adverse effect in a human subject being treated for a neurological condition, comprising orally administering once a day to said human subject a pharmaceutical composition in a unit dosage form 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 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 said 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 hours to 6 hours of administration of said pharmaceutical composition and said immediate release form of said first drug to a human subject in the same single dose human pharmacokinetic study;
• and
• wherein the neurological condition is selected from the group consisting of Alzheimer's disease and dementia, wherein the oral administration of the pharmaceutical composition to the human subject is less likely to cause an adverse effect of the first drug in the human subject than is oral administration of an equal dose of the immediate release form of the first drug.