METHODS OF ADMINISTERING AMANTADINE COMPOSITIONS
Methods of administration of amantadine to improve movement disorders are described, as well as compositions suitable therefor.
1 . A method of improving gait in a human subject, comprising orally administering to said subject once daily, a dose comprising (i) 220 mg to 600 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof and (ii) at least one excipient.
2 . A method of treating a hypokinetic movement disorder in a human subject, comprising orally administering to said subject once daily, a dose comprising (i) 220 mg to 600 mg of a drug selected from the group consisting of amantadine and pharmaceutically acceptable salts thereof and (ii) at least one excipient.
3 . The method of any one of claim 1 or 2 wherein the human subject has multiple sclerosis.
4 . The method of any one of claim 1 or 2 , wherein the human subject has experienced a stroke.
5 . The method of any one of claims 1 to 4 , wherein the dose additionally comprises one or more drugs selected from the group consisting of 4-aminopyridine, baclofen, dextromethorphan, dimethyl fumarate, fingolimod, methylphenidate, and teriflunomide, tetrabenizine, and tizanidine.
6 . The method of any one of claims 1 to 5 , wherein at least one excipient is a release modifying excipient.
7 . The method of any one of claims 1 to 5 , wherein at least one of said excipients modifies the release of the amantadine or pharmaceutically acceptable salt thereof to provide an extended release form, and wherein administration of the dose provides a) a Tmax for amantadine of 5 to 18 hours, b) a Cmax of 1.0 to 2.8 ng/ml per mg amantadine, and c) an AUC 0-inf of 40 to 75 ng*hr/ml per mg amantadine as measured in a single dose human pharmacokinetic study.
8 . The method of claim 5 , wherein said drug is provided in an extended release form.
9 . The method of any one of claim 1 or 2 , wherein said dose is administered in the morning and the composition provides a median Tmax of 5 to 9 hours as determined from a single dose, fasted, human pharmacokinetic study.
10 . The method of any one of claim 1 or 2 , wherein said dose is administered 0 to 4 hours before bedtime and the composition provides a median Tmax of 10 to 18 hours as determined from a single dose, fasted, human pharmacokinetic study.
11 . The method of any one claim 1 or 2 , wherein once daily administration of said dose provides a steady state C-ave-day/C-ave-night ratio of 1.1 to 2.0.
12 . The method of claim 9 , wherein the Cmax/Cmin ratio at steady state is 1.3-3.
13 . The method of claim 10 , wherein the Cmax/Cmin ratio at steady state is 1.3-3.