Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects

• US 9,707,191 B2
• Filed: 09/29/2016
• Issued: 07/18/2017
• 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:
  US15/280,938
• Publication Number:
  US 20170014357A1
• Time in Patent Office: 292 Days
• Field of Search: None
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031

Abstract

This disclosure relates to methods administering various compounds in conjunction with dextromethorphan to a human being. Dosage forms, drug delivery systems, and methods related to dextromethorphan or dextrorphan and bupropion, hydroxybupropion, erythrohydroxybupropion, threohydroxybupropion, or a metabolite or prodrug of any of these compounds are also disclosed.

Claims

1. A method of reducing a trough effect of a dextromethorphan in a human subject, wherein the human subject is an extensive metabolizer of the dextromethorphan in need of treatment with the dextromethorphan, comprising co-administering to the human subject a daily dose of a combination, wherein the combination comprises:

1) a hydroxybupropion, a threohydroxybupropion, an erythrohydroxybupropion or a bupropion, and

2) the dextromethorphan,

once a day for at least nine consecutive days or twice a day for at least nine consecutive days,

wherein the daily dose of the dextromethorphan is about 40 mg to about 350 mg, and co-administration of the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion, and the dextromethorphan results in a first C_min of the dextromethorphan that is at least about 20 ng/mL, on the ninth day of consecutive administration, and the first C_min of the dextromethorphan is at least about 20 times a second C_min of the dextromethorphan that would result from administering the daily dose of the dextromethorphan without the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion to the human subject for nine consecutive days.

2. The method of claim 1, wherein the daily dose of the dextromethorphan is about 42 mg to about 190 mg.

3. The method of claim 1, wherein the daily dose of the dextromethorphan is about 46 mg to about 100 mg.

4. The method of claim 1, wherein a single dose of the dextromethorphan is about 42 mg to about 44 mg.

5. The method of claim 1, wherein a single dose of the dextromethorphan is about 44 mg to about 46 mg.

6. The method of claim 1, wherein a single dose of the dextromethorphan is about 46 mg to about 48 mg.

7. The method of claim 1, wherein the first C_min of the dextromethorphan is at least about 30 times the second C_min of the dextromethorphan.

8. The method of claim 1, wherein the first C_min of the dextromethorphan is at least about 40 times the second C_min of the dextromethorphan.

9. The method of claim 5, wherein the first C_min of the dextromethorphan is at least about 50 times the second C_min of the dextromethorphan.

10. The method of claim 1, wherein the first C_min of the dextromethorphan is about 20 ng/mL to about 30 ng/mL.

11. The method of claim 1, wherein the first C_min of the dextromethorphan is about 55 ng/mL to about 70 ng/mL.

12. The method of claim 1, wherein the first C_min of the dextromethorphan is about 70 ng/mL to about 90 ng/mL.

13. The method of claim 5, wherein the first C_min of the dextromethorphan is about 115 ng/mL to about 120 ng/mL.

14. The method of claim 1, wherein the first C_min of the dextromethorphan is about 170 ng/mL to about 200 ng/mL.

15. The method of claim 1, wherein the first C_min of the dextromethorphan is about 20 ng/mL to about 10,000 ng/mL.

16. The method of claim 1, wherein the daily dose of the bupropion is about 40 mg to about 300 mg.

17. The method of claim 1, wherein the daily dose of the bupropion is about 70 mg to about 220 mg.

18. The method of claim 1, wherein a single dose of the bupropion is about 70 mg to about 105 mg.

19. The method of claim 5, wherein a single dose of the bupropion is about 105 mg to about 150 mg.

20. The method of claim 1, wherein the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, the bupropion or the dextromethorphan is deuterium-modified.

21. The method of claim 20, wherein the dextromethorphan is deuterium-modified.

22. The method of claim 1, wherein the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion, and the dextromethorphan, are co-administered as a solid or liquid, in a single oral dosage form.

23. The method of claim 22, wherein the single oral dosage form is a solid.

24. The method of claim 23, wherein the single solid oral dosage form further comprises a binder, a disintegrating agent or a lubricant.

25. The method of claim 23, wherein the single solid oral dosage form is a tablet, a troche, a pill or a capsule.

26. The method of claim 22, wherein the single oral dosage form is a liquid.

27. The method of claim 26, wherein the single liquid dosage form comprises a liquid or solid phase dispersion of the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion, and the dextromethorphan.

28. The method of claim 12, wherein the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion, and the dextromethorphan are co-administered to the human subject once a day for at least 30 consecutive days or twice a day for at least 30 consecutive days.

29. The method of claim 1, wherein the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion or the bupropion, and the dextromethorphan are co-administered to the human subject once a day for at least 60 consecutive days or twice a day for at least 60 consecutive days.

30. The method of claim 1, wherein the bupropion comprises an enantiomeric excess of R-bupropion or S-bupropion.