DOSAGE FORMS AND METHODS FOR ENANTIOMERICALLY ENRICHED OR PURE BUPROPION
This disclosure relates to dosage forms containing an enantiomerically enriched or pure bupropion such as enantiomeric excess of (S)-bupropion, enantiomerically enriched (S)-bupropion, or enantiomerically pure (S)-bupropion and methods of using these dosage forms. These dosage forms may be administered to human beings in a reduced amount as compared to the amount of racemic bupropion that would be administered in the same situation.
1 . A method of providing therapeutically effective plasma levels of (R,R)-hydroxybupropion comprising orally administering, one or two times per day, a dosage form containing (S)-bupropion that is at least 95% enantiomerically pure, to a human being in need of treatment with (R,R)-hydroxybupropion, wherein (R,R)-hydroxybupropion is at least 97% of the total amount of (R,R)-hydroxybupropion and (S,S)-hydroxybupropion present in the plasma of the human being, and wherein the method achieves a C max of (R,R)-hydroxybupropion that is at least about 500 ng/mL in the human being.
2 . The method of claim 1 , wherein the dosage form is orally administered once daily.
3 . The method of claim 2 , wherein the dosage form contains about 150 mg to about 180 mg of the (S)-bupropion.
4 . The method of claim 1 , wherein the dosage form is orally administered twice daily.
5 . The method of claim 4 , wherein the dosage form contains about 70 mg to about 80 mg of the (S)-bupropion.
6 . The method of claim 1 , wherein the dosage form is orally administered for at least 8 consecutive days.
7 . The method of claim 1 , wherein the dosage form is orally administered for at least 14 consecutive days.
8 . The method of claim 1 , wherein the dosage form is orally administered for at least 21 consecutive days.
9 . The method of claim 1 , wherein the dosage form is orally administered for at least 28 consecutive days.
10 . The method of claim 1 , wherein the method achieves an AUC 0-12 of (S)-bupropion in the human being that is at least about 400 ng·hr/mL.
11 . The method of claim 1 , wherein the method achieves an AUC 0-12 of (S)-bupropion in the human being that is about 500 ng·hr/mL to about 900 ng·hr/mL.
12 . The method of claim 8 , wherein the method achieves a C max of (S)-bupropion in the human being that is about 60 ng/mL to about 140 ng/mL.
13 . The method of claim 1 , wherein the dosage form provides sustained release of (S)-bupropion.
14 . The method of claim 1 , wherein:
the human being is selected for being in need of a target AUC 0-24 of (R,R)-hydroxybupropion, wherein the target AUC 0-24 of (R,R)-hydroxybupropion is an AUC 0-24 of (R,R)-hydroxybupropion that would result from orally administering, to the human being, a daily dose of racemic bupropion that is about 150 mg to about 200 mg; and
a daily dose of the (S)-bupropion that is about 60 mg to about 120 mg is orally administered to the human being to achieve the target AUC 0-24 of (R,R)-hydroxybupropion; and
the daily dose of the (S)-bupropion is about 40% to about 60% of the daily dose of racemic bupropion.
15 . The method of claim 14 , wherein the target AUC 0-24 of (R,R)-hydroxybupropion is effective in treating attention deficit/hyperactivity disorder.
16 . The method of claim 1 , wherein:
the human being is selected for being in need of a target AUC 0-24 of (R,R)-hydroxybupropion, wherein the target AUC 0-24 of (R,R)-hydroxybupropion is an AUC 0-24 of (R,R)-hydroxybupropion that would result from orally administering, to the human being, a daily dose of racemic bupropion that is about 200 mg to about 250 mg; and
a daily dose of the (S)-bupropion that is about 80 mg to about 150 mg is orally administered to the human being to achieve the target AUC 0-24 of (R,R)-hydroxybupropion; and
the daily dose of the (S)-bupropion is about 40% to about 60% of the daily dose of racemic bupropion.
17 . The method of claim 16 , wherein the target AUC 0-24 of (R,R)-hydroxybupropion is effective in treating attention deficit/hyperactivity disorder.
18 . The method of claim 1 , wherein:
the human being is selected for being in need of a target AUC 0-24 of (R,R)-hydroxybupropion, wherein the target AUC 0-24 of (R,R)-hydroxybupropion is an AUC 0-24 of (R,R)-hydroxybupropion that would result from orally administering, to the human being, a daily dose of racemic bupropion that is about 250 mg to about 300 mg; and
a daily dose of the (S)-bupropion that is about 100 mg to about 180 mg is orally administered to the human being to achieve the target AUC 0-24 of (R,R)-hydroxybupropion; and
the daily dose of the (S)-bupropion is about 40% to about 60% of the daily dose of racemic bupropion.
19 . The method of claim 18 , wherein the target AUC 0-24 of (R,R)-hydroxybupropion is effective in treating attention deficit/hyperactivity disorder.
20 . The method of claim 1 , wherein:
the human being is selected for being in need of a target AUC 0-24 of (R,R)-hydroxybupropion, wherein the target AUC 0-24 of (R,R)-hydroxybupropion is an AUC 0-24 of (R,R)-hydroxybupropion that would result from orally administering, to the human being, a daily dose of racemic bupropion that is about 300 mg to about 350 mg; and
a daily dose of the (S)-bupropion that is about 120 mg to about 210 mg is orally administered to the human being to achieve the target AUC 0-24 of (R,R)-hydroxybupropion; and
the daily dose of the (S)-bupropion is about 40% to about 60% of the daily dose of racemic bupropion.
21 . The method of claim 20 , wherein the target AUC 0-24 of (R,R)-hydroxybupropion is effective in treating attention deficit/hyperactivity disorder.
22 . The method of claim 1 , wherein:
the human being is selected for being in need of a target AUC 0-24 of (R,R)-hydroxybupropion, wherein the target AUC 0-24 of (R,R)-hydroxybupropion is an AUC 0-24 of (R,R)-hydroxybupropion that would result from orally administering, to the human being, a daily dose of racemic bupropion that is about 350 mg to about 400 mg; and
a daily dose of the (S)-bupropion that is about 140 mg to about 240 mg is orally administered to the human being to achieve the target AUC 0-24 of (R,R)-hydroxybupropion; and
the daily dose of the (S)-bupropion is about 40% to about 60% of the daily dose of racemic bupropion.
23 . The method of claim 22 , wherein the target AUC 0-24 of (R,R)-hydroxybupropion is effective in treating attention deficit/hyperactivity disorder.
24 . The method of claim 1 , wherein:
the human being is selected for being in need of a target AUC 0-24 of (R,R)-hydroxybupropion, wherein the target AUC 0-24 of (R,R)-hydroxybupropion is an AUC 0-24 of (R,R)-hydroxybupropion that would result from orally administering, to the human being, a daily dose of racemic bupropion that is about 400 mg to about 450 mg; and
a daily dose of the (S)-bupropion that is about 160 mg to about 270 mg is orally administered to the human being to achieve the target AUC 0-24 of (R,R)-hydroxybupropion; and
the daily dose of the (S)-bupropion is about 40% to about 60% of the daily dose of racemic bupropion.
25 . The method of claim 24 , wherein the target AUC 0-24 of (R,R)-hydroxybupropion is effective in treating attention deficit/hyperactivity disorder.