Compositions and methods for increasing dextromethorphan plasma levels and related pharmacodynamic effects
View Patent ↗This disclosure relates to methods of increasing dextromethorphan plasma levels comprising co-administering hydroxybupropion, or a prodrug thereof, and dextromethorphan to a human being in need of treatment with dextromethorphan. Dosage forms, drug delivery systems, and methods related to dextromethorphan and hydroxybupropion or a prodrug of bupropion are also disclosed.
1. A method of increasing dextromethorphan plasma levels in the human being that is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, comprising co-administering hydroxybupropion or bupropion with dextromethorphan to a human being once or twice a day for at least eight consecutive days, wherein the daily dose of dextromethorphan is about 40 mg to about 600 mg, and co-administering hydroxybupropion or bupropion with dextromethorphan results in an AUC 0-12 of dextromethorphan that, on the eighth day, is at least about 20 times the AUC 0-12 that would be achieved by administering the same amount of dextromethorphan without hydroxybupropion or bupropion for eight consecutive days.
2. The method of claim 1 , wherein the daily dose of dextromethorphan is about 60 mg to about 260 mg.
3. The method of claim 1 , wherein the daily dose of dextromethorphan is about 60 mg to about 120 mg.
4. The method of claim 1 , wherein the daily dose of dextromethorphan is about 60 mg to about 100 mg.
5. The method of claim 1 , wherein the dextromethorphan is co-administered in a dosage form that contains about 40 mg to about 50 mg of dextromethorphan.
6. The method of claim 4 , wherein the dextromethorphan is co-administered in a dosage form that contains about 40 mg to about 50 mg of dextromethorphan.
7. The method of claim 1 , wherein the hydroxybupropion or bupropion and dextromethorphan are co-administered together in a single solid oral dosage form.
8. The method of claim 7 , wherein the single solid oral dosage form further comprises a binder, a disintegrating agent, or a lubricant.
9. The method of claim 1 , further comprising co-administering hydroxybupropion or bupropion with dextromethorphan to the human being once or twice a day for at least 30 consecutive days.
10. The method of claim 1 , further comprising co-administering hydroxybupropion or bupropion with dextromethorphan to the human being once or twice a day for at least 60 consecutive days.
11. The method of claim 1 , further comprising co-administering hydroxybupropion or bupropion with dextromethorphan to the human being once or twice a day for at least 180 consecutive days.
12. The method of claim 1 , comprising co-administering hydroxybupropion or bupropion with dextromethorphan to the human being twice a day.
13. The method of claim 1 , comprising co-administering hydroxybupropion or bupropion with dextromethorphan to the human being once a day.
14. The method of claim 1 , wherein, on the eighth day, the AUC 0-12 of hydroxybupropion is at least about 3000 ng·hr/mL.
15. The method of claim 1 , wherein, on the eighth day, the AUC 0-12 of hydroxybupropion is at least about 7000 ng·hr/mL.
16. The method of claim 1 , wherein the hydroxybupropion, bupropion, or dextromethorphan is deuterium modified.
17. The method of claim 16 , wherein the dextromethorphan is deuterium modified.