Method of administering amantadine prior to a sleep period
Methods of nighttime administration of amantadine to reduce sleep disturbances in patient undergoing treatment with amantadine are described, as well as compositions of extended release amantadine that are suitable for nighttime administration.
1. A method of treating a patient with Parkinson's disease, comprising administering once daily, 0 to 4 hours before bedtime, to said patient with Parkinson's disease, a pharmaceutical composition comprising: (i) 220 mg to 455 mg of a drug selected from the group consisting of amantadine and a pharmaceutically acceptable salt thereof; and (ii) one or more excipients, wherein at least one of said one or more excipients modifies the release of said drug to provide an extended release dosage form,
wherein ON time without troublesome dyskinesia is increased in said patient with Parkinson's disease, and
wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Tmax for the drug is 8 to 20 hours.
2. The method of claim 1 , wherein said increased ON time without troublesome dyskinesia is determined from a Parkinson's disease home diary.
3. The method of claim 1 , wherein said Tmax is 9 to 18 hours.
4. The method of claim 1 , wherein said Tmax is 11 to 18 hours.
5. The method of claim 1 , wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the AUC 0-inf for the drug is 40 to 75 ng*hr/ml per mg of the drug.
6. The method of claim 1 , wherein when said pharmaceutical composition is dosed in a multiple dose, fasted, human pharmacokinetic study in healthy subjects, the steady state AUC 0-24 for the drug is 44 to 83 ng*hr/ml per mg of the drug.
7. The method of claim 1 , wherein said pharmaceutical composition is administered to said patient once daily, 0 to 3 hours before bedtime.
8. The method of claim 1 , wherein said pharmaceutical composition comprises 1 or 2 unit dosage forms.
9. The method of claim 1 , wherein said pharmaceutical composition comprises one, two, or three capsules.
10. A method of treating a patient with Parkinson's disease, comprising administering once daily, 0 to 4 hours before bedtime, to said patient with Parkinson's disease, a pharmaceutical composition comprising: (i) 220 mg to 445 mg of a drug selected from the group consisting of amantadine and a pharmaceutically acceptable salt thereof; and (ii) one or more excipients, wherein at least one of said one or more excipients modifies the release of said drug to provide an extended release dosage form,
wherein ON time without troublesome dyskinesia is increased in said patient with Parkinson's disease, and
wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Cmax for the drug is 1.0 to 2.8 ng/ml per mg of the drug and the AUC 0-inf for the drug is 40 to 75 ng*h/ml per mg of the drug.
11. The method of claim 10 , wherein said increased ON time without troublesome dyskinesia is determined from a Parkinson's disease home diary.
12. The method of claim 10 , wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Tmax for the drug is 8 to 18 hours.
13. The method of claim 10 , wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Tmax for the drug is 9 to 18 hours.
14. The method of claim 10 , wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Tmax for the drug is 11 to 18 hours.
15. The method of claim 10 , wherein when said pharmaceutical composition is dosed in a multiple dose, fasted, human pharmacokinetic study in healthy subjects, the steady state AUC 0-24 for the drug is 44 to 83 ng*hr/ml per mg of the drug.
16. The method of claim 10 , wherein said pharmaceutical composition is administered to said patient once daily, 0 to 3 hours before bedtime.
17. The method of claim 10 , wherein said pharmaceutical composition comprises 1 or 2 unit dosage forms.
18. The method of claim 10 , wherein said pharmaceutical composition comprises one, two, or three capsules.
19. The method of claim 10 , wherein said drug is a pharmaceutically acceptable salt of amantadine.
20. The method of claim 10 , wherein said drug is amantadine hydrochloride.
21. The method of claim 10 , wherein said pharmaceutical composition is selected from the group consisting of one unit dosage form comprising 340 mg of said drug and two unit dosage forms each comprising 170 mg of said drug.
22. The method of claim 21 , wherein said drug is a pharmaceutically acceptable salt of amantadine.
23. The method of claim 21 , wherein said drug is amantadine hydrochloride.
24. The method of claim 1 , wherein said drug is a pharmaceutically acceptable salt of amantadine.
25. The method of claim 1 , wherein said drug is amantadine hydrochloride.
26. The method of claim 1 , wherein said pharmaceutical composition is selected from the group consisting of one unit dosage form comprising 340 mg of said drug and two unit dosage forms each comprising 170 mg of said drug.
27. The method of claim 26 , wherein said drug is a pharmaceutically acceptable salt of amantadine.
28. The method of claim 26 , wherein said drug is amantadine hydrochloride.
29. The method of claim 1 , wherein when said pharmaceutical composition is dosed in a single dose, fasted, human pharmacokinetic study in healthy subjects, the Cmax for the drug is 1.0 to 2.8 ng/ml per mg of the drug.
30. The method of claim 29 , wherein the Cmax for the drug is 1.0 to 2.4 ng/ml per mg of the drug.
31. The method of claim 10 , wherein the Cmax for the drug is 1.0 to 2.4 ng/ml per mg of the drug.