Composition and method for treating neurological disease
View Patent ↗The invention provides methods and compositions for treating or preventing neurological disorders.
1. A method of treating a patient with Parkinson's disease comprising orally administering to the patient a first agent and once-daily orally administering to the patient a second agent, said first agent comprising a therapeutically effective amount of levodopa/carbidopa in an immediate release form and said second agent consisting essentially of a therapeutically effective amount of amantadine or pharmaceutically acceptable salt thereof in an amount ranging from 200 mg to 500 mg in an extended release form, wherein:
the amantadine or pharmaceutically acceptable salt thereof provides change in plasma concentration as a function of time (dC/dT) over a defined period between 0 and 4 hours after administration that is less than about 40% of the dC/dT of the same quantity of an immediate release form of amantadine over said defined time period, wherein the dC/dT is measured in a single dose human pharmacokinetic study.
2. The method of claim 1 wherein the amantadine is administered at a dose of 300 to 500 mg per day.
3. A method of reducing amantadine-related neurotoxicity in a patient with Parkinson's disease comprising orally administering to the patient a first agent and once-daily orally administering to the patient a second agent, said first agent comprising a therapeutically effective amount of levodopa/carbidopa in an immediate release form and said second agent consisting essentially of a therapeutically effective amount of amantadine or pharmaceutically acceptable salt thereof in an amount ranging from 200 mg to 500 mg in an extended release form, wherein:
the extended release amantadine or pharmaceutically acceptable salt thereof provides a change in amantadine plasma concentration as a function of time (dC/dT) over a defined time period between 0 and 4 hours after administration that is less than about 40% of the dC/dT of the same quantity of an immediate release form of amantadine over said defined time period, wherein the dC/dT is measured in a single dose human pharmacokinetic study.
4. The method of claim 3 , wherein the side effect is dizziness.
5. The method of claim 3 , wherein the amantadine is administered at a dose of 300 to 500 mg per day.
6. A method of reducing levodopa/carbidopa-related CNS side effects in a patient with Parkinson's disease comprising orally administering to the patient a first agent and once-daily orally administering to the patient a second agent, said first agent comprising a therapeutically effective amount of levodopa/carbidopa in an immediate release form and said second agent consisting essentially of a therapeutically effective amount of amantadine or pharmaceutically acceptable salt thereof in an amount ranging from 200 mg to 500 mg in an extended release form, wherein:
the extended release amantadine or pharmaceutically acceptable salt thereof provides a change in amantadine plasma concentration as a function of time (dC/dT) over a defined time period between 0 and 4 hours after administration that is less than about 40% of the dC/dT of the same quantity of an immediate release form of amantadine over said defined time period, wherein the dC/dT is measured in a single dose human pharmacokinetic study.
7. The method claim 3 , wherein the levodopa/carbidopa-related side effects are dyskinesias.
8. The method of claim 3 , wherein the amantadine is administered at a dose of 300 to 500 mg per day.