Compositions and methods comprising erythrohydroxybupropion and related compounds for improving the efficacy of dextromethorphan

• US 9,375,429 B2
• Filed: 10/08/2015
• Issued: 06/28/2016
• Est. Priority Date: 11/05/2013
• Status: Active Grant

• Current Assignee: Antecip Bioventures II LLC
• Original Assignee: Antecip Bioventures II LLC
• Inventors: Tabuteau, Herriot
• Primary Examiner(s): Baek, Bong-Sook
• Application Number:
  US14/879,002
• Publication Number:
  US 20160030421A1
• Time in Patent Office: 264 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/4748 forming part of bridged ring systems strychnine A61K31/475; morphinan derivatives A61K31/485
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine

Abstract

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.

Claims

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.