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

• US 10,105,361 B2
• Filed: 06/13/2017
• Issued: 10/23/2018
• 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): Barsky, Jared
• Application Number:
  US15/621,882
• Publication Number:
  US 20170281617A1
• Time in Patent Office: 497 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 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/15 Oximes (>C=N—O—); Hydrazines (>N—N<); Hydrazones (>N—N=) ; Imines (C—N=C)
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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, comprising co-administering a dose of a combination once a day for 1, 2, 3, 4, 5, 6, or 7 days prior to co-administering the dose of the combination twice a day for at least eight consecutive days to the human subject, wherein the combination comprises:

1) a bupropion; and

2) the dextromethorphan; and

wherein;

the human subject is an extensive metabolizer of the dextromethorphan in need of treatment with the dextromethorphan;

the dose of the bupropion is about 50 mg to about 500 mg;

co-administration of the combination results in a first C_min of the dextromethorphan that is at least about 20 ng/mL, on the eighth day of twice a day consecutive co-administration; and

the first C_min of the dextromethorphan is at least about 20 times higher than a second C_min of the dextromethorphan that would result from administering the dextromethorphan without the bupropion to the human subject for eight days of twice a day consecutive administration.

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

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

4. The method of claim 1, wherein the first C_min of the dextromethorphan is at least about 40 ng/mL.

5. The method of claim 1, wherein the first C_min of the dextromethorphan is at least about 65 ng/mL.

6. The method of claim 1, wherein the first C_min of the dextromethorphan is about 30 ng/mL to about 40 ng/mL.

7. The method of claim 1, wherein the first C_min of the dextromethorphan is about 40 ng/mL to about 50 ng/mL.

8. The method of claim 1, wherein the first C_min of the dextromethorphan is about 60 ng/mL to about 65 ng/mL.

9. The method of claim 1, wherein the first C_min of the dextromethorphan is about 65 ng/mL to about 70 ng/mL.

10. The method of claim 1, wherein the combination is orally co-administered.

11. The method of claim 1, wherein the dextromethorphan is deuterium modified.

12. The method of claim 1, wherein the bupropion is deuterium modified.

13. The method of claim 1, wherein the combination is co-administered for at least 60 days.

14. The method of claim 1, wherein the dose of the bupropion is about 90 mg to about 105 mg.

15. The method of claim 1, wherein the dose of the bupropion is about 105 mg to about 110 mg.

16. The method of claim 1, wherein the dose of the dextromethorphan is about 42 mg to about 46 mg.

17. The method of claim 1, wherein the dose of the dextromethorphan is about 44 mg to about 48 mg.

18. The method of claim 14, wherein the dose of the dextromethorphan is about 42 mg to about 46 mg.

19. The method of claim 15, wherein the dose of the dextromethorphan is about 44 mg to about 48 mg.

20. The method of claim 1, wherein a daily dose of the bupropion during twice a day co-administration is about 150 mg to about 300 mg.

21. The method of claim 1, wherein a daily dose of the bupropion during twice a day co-administration is about 200 mg to about 250 mg.

22. The method of claim 1, wherein a daily dose of the dextromethorphan during twice a day co-administration is about 55 mg to about 120 mg.

23. The method of claim 1, wherein a daily dose of the dextromethorphan during twice a day co-administration is about 60 mg to about 100 mg.

24. The method of claim 20, wherein the daily dose of the dextromethorphan during twice a day co-administration is about 55 mg to about 120 mg.

25. The method of claim 21, wherein the daily dose of the dextromethorphan during twice a day co-administration is about 60 mg to about 100 mg.

26. The method of claim 1, wherein the dose is co-administered orally.

27. The method of claim 26, wherein the combination is incorporated with an excipient into a tablet, a troche, a capsule, an elixir, a suspension, a syrup, or a wafer.

28. The method of claim 1, wherein the combination further comprises one or more of a binder, an excipient, a disintegrating agent, a lubricant, a sweetening agent, or a flavoring agent.

29. The method of claim 27, wherein the dose is co-administered in a dosage form that provides sustained release of the bupropion.

30. The method of claim 1, wherein the human subject has previously taken at least 1 antidepressant therapy, and then discontinued.