Compositions and methods comprising erythrohydroxybupropion and related compounds for improving the efficacy of dextromethorphan
View Patent ↗This disclosure relates to methods of improving the efficacy of dextromethorphan, or providing beneficial pharmacokinetic effects to dextromethorphan, comprising co-administering erythrohydroxybupropion, or a prodrug thereof, and dextromethorphan to a human being. Dosage forms, drug delivery systems, and methods related to dextromethorphan and erythrohydroxybupropion or a prodrug of erythrohydroxybupropion are also disclosed.
1. A method of increasing dextromethorphan plasma levels in a human being that is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, comprising co-administering a) erythrohydroxybupropion or bupropion with b) dextromethorphan to the 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 erythrohydroxybupropion 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 erythrohydroxybupropion 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 40 mg to about 100 mg.
5. The method of claim 1 , wherein 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 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 erythrohydroxybupropion 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 erythrohydroxybupropion 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 erythrohydroxybupropion 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 erythrohydroxybupropion 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 erythrohydroxybupropion or bupropion with dextromethorphan to the human being twice a day.
13. The method of claim 1 , comprising co-administering erythrohydroxybupropion 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 erythrohydroxybupropion is at least about 200 ng·hr/mL.
15. The method of claim 1 , wherein, on the eighth day, the AUC 0-12 of erythrohydroxybupropion is at least about 400 ng·hr/mL.
16. The method of claim 1 , wherein erythrohydroxybupropion, bupropion, or dextromethorphan is deuterium-modified.
17. The method of claim 16 , wherein dextromethorphan is deuterium-modified.
18. The method of claim 1 , wherein erythrohydroxybupropion or bupropion and dextromethorphan are independently administered either orally or parenterally.
19. The method of claim 18 , wherein erythrohydroxybupropion or bupropion and dextromethorphan are orally administered in a solid or liquid dosage form.
20. The method of claim 19 , wherein the solid dosage form is a tablet, a troche, a pill, or a capsule.
21. The method of claim 20 , wherein bupropion and dextromethorphan independently comprise at least 5% (w/w) of the solid dosage form.
22. The method of claim 19 , wherein bupropion and dextromethorphan independently comprise at least 0.0001% (w/v) of the liquid dosage form.
23. The method of claim 8 , wherein the binder comprises gum tragacanth, acacia, corn starch, or gelatin.
24. The method of claim 8 , wherein the disintegrating agent comprises corn starch, potato starch, or alginic acid.
25. The method of claim 8 , wherein the lubricant comprises magnesium stearate.
26. The method of claim 1 , wherein erythrohydroxybupropion or bupropion and dextromethorphan are co-administered as two separate dosage forms.
27. The method of claim 18 , wherein the liquid dosage form comprises a liquid or a solid phase dispersion.