METHODS OF MODULATING TETRABENAZINE METABOLITES PLASMA LEVELS USING BUPROPION
This disclosure relates to methods administering bupropion, such as S-bupropion or R-bupropion, in conjunction with tetrabenazine, alpha-dihydrotetrabenazine, or beta-dihydrotetrabenazine to a human being. Dosage forms, drug delivery systems, and methods related to tetrabenazine, alpha-dihydrotetrabenazine, or beta-dihydrotetrabenazine and bupropion, such as S-bupropion or R-bupropion, are also disclosed.
1 . A dosage form comprising a tetrabenazine and a bupropion.
2 . The dosage form of claim 1 , comprising about 5 mg to about 20 mg of the tetrabenazine.
3 . The dosage form of claim 2 , comprising about 70 mg to about 140 mg of the bupropion.
4 . The dosage form of claim 1 , comprising about 70 mg to about 140 mg of the bupropion.
5 . The dosage form of claim 1 , comprising about 10 mg to about 15 mg of the tetrabenazine.
6 . The dosage form of claim 5 , comprising about 90 mg to about 110 mg of the bupropion.
7 . The dosage form of claim 1 , comprising about 90 mg to about 110 mg of the bupropion.
8 . The dosage form of claim 7 , which provides sustained release of the bupropion.
9 . The dosage form of claim 7 , having a weight ratio of tetrabenazine to bupropion that is about 0.1 to about 0.3.
10 . The dosage form of claim 1 , which provides sustained release of the bupropion.
11 . The dosage form of claim 1 , having a weight ratio of tetrabenazine to bupropion that is about 0.1 to about 0.3.
12 . The dosage form of claim 1 , wherein the tetrabenazine is not deuterium-modified.
13 . The dosage form of claim 1 , wherein the bupropion is not deuterium-modified.
14 . The dosage form of claim 1 , wherein the bupropion has an enantiomeric excess of S-bupropion.
15 . The dosage form of claim 1 , wherein the bupropion has an enantiomer excess of at least 97% of S-bupropion.
16 . The dosage form of claim 1 , which has the property that administering the dosage form twice a day for eight consecutive days to a healthy human subject results in the healthy human subject having an AUC 0-inf of alpha-dihydrotetrabenazine that is at least about 400 ng·hr/mL on the eighth day that the dosage form is administered.
17 . The dosage form of claim 1 , which has the property that administering the dosage form twice a day for eight consecutive days to a healthy human subject results in the healthy human subject having an AUC 0-inf of beta-dihydrotetrabenazine that is at least about 400 ng·hr/mL on the eighth day that the dosage form is administered.
18 . The dosage form of claim 1 , comprising about 70 mg to about 100 mg of the bupropion.
19 . The dosage form of claim 1 , comprising about 100 mg to about 140 mg of the bupropion.
20 . The dosage form of claim 1 , comprising about 9 mg to about 12 mg of the tetrabenazine.
21 . The dosage form of claim 1 , comprising about 12 mg to about 15 mg of the tetrabenazine.