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

• US 9,474,731 B1
• Filed: 06/14/2016
• Issued: 10/25/2016
• 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:
  US15/182,253
• Publication Number:
  US 20160317476A1
• Time in Patent Office: 133 Days
• Field of Search: None
• US Class Current: 1/1
• 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

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 increasing the metabolic lifetime of dextromethorphan, comprising co-administering dextromethorphan with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion, to a human being who is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, once or twice a day for at least eight consecutive days, wherein bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion is administered in an amount that results in a C_min of dextromethorphan in the human being, on the eighth day, that is at least about 20 ng/mL and is at least 20 times the C_min that would have been achieved by administering the same amount of dextromethorphan without bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion for eight consecutive days, and wherein dextromethorphan is present in the body of the human being at the same time as bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion.

2. The method of claim 1, wherein dextromethorphan is orally co-administered with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion.

3. The method of claim 2, wherein dextromethorphan is orally co-administered with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion in a single dosage form.

4. The method of claim 3, wherein the oral dosage form is solid.

5. The method of claim 4, wherein the solid, oral dosage form is a tablet, a troche, a pill, or a capsule.

6. The method of claim 1, wherein dextromethorphan is co-administered once a day with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion.

7. The method of claim 1, wherein dextromethorphan is co-administered twice a day with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion.

8. The method of claim 7, wherein about 40 mg to about 100 mg of dextromethorphan is administered.

9. The method of claim 1, wherein about 50 mg to about 150 mg of bupropion is administered.

10. The method of claim 9, wherein bupropion is administered twice a day.

11. The method of claim 1, wherein dextromethorphan is co-administered with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion for at least 14 days.

12. The method of claim 1, wherein dextromethorphan is co-administered with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion for at least 30 days.

13. The method of claim 1, wherein dextromethorphan is co-administered with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion for at least 60 days.

14. The method of claim 1, wherein dextromethorphan is co-administered with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion for at least 90 days.

15. The method of claim 11, wherein on the tenth day of co-administration, the C_min of dextromethorphan is at least 30 times the C_min of dextromethorphan that would have been achieved by administering the same amount of dextromethorphan without bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion, for ten consecutive days.

16. A method of increasing the metabolic lifetime of dextromethorphan, comprising co-administering dextromethorphan with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion, to a human being who is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, once or twice a day for at least eight consecutive days, wherein bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion is administered in an amount that results in an C_min of dextromethorphan in the human being, on the eighth day, that is at least about 30 ng/mL and is at least 20 times the C_min that would have been achieved by administering the same amount of dextromethorphan without bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion for eight consecutive days, and wherein dextromethorphan is present in the body of the human being at the same time as bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion.

17. The method of claim 16, wherein dextromethorphan is co-administered with bupropion or hydroxybupropion.

18. The method of claim 16, wherein dextromethorphan is co-administered with bupropion or erythrohydroxybupropion.

19. The method of claim 16, wherein dextromethorphan is co-administered with bupropion or threohydroxybupropion.

20. The method of claim 16, wherein the bupropion, hydroxybupropion, erythrohydroxybupropion, threohydroxybupropion, or dextromethorphan is deuterium-modified.

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

22. A method of increasing the metabolic lifetime of dextromethorphan, comprising co-administering dextromethorphan with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion, to a human being who is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, once or twice a day for at least eight consecutive days, wherein bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion is administered in an amount that results in an C_min of dextromethorphan in the human being, on the eighth day, that is at least about 40 ng/mL and is at least 30 times the C_min that would have been achieved by administering the same amount of dextromethorphan without bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion for eight consecutive days, and wherein dextromethorphan is present in the body of the human being at the same time as bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion.

23. The method of claim 22, wherein on the eighth day of co-administration, the C_min of dextromethorphan is at least 50 ng/mL.

24. The method of claim 22, wherein on the eighth day of co-administration, the C_min of dextromethorphan is at least 60 ng/mL.

25. The method of claim 24, wherein on the eighth day of co-administration, the C_max of dextromethorphan is at least 80 ng/mL.

26. The method of claim 22, wherein dextromethorphan is co-administered with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion for at least 14 days.

27. The method of claim 22, wherein dextromethorphan is co-administered with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion, for at least 30 days.

28. The method of claim 22, wherein dextromethorphan is co-administered with bupropion, hydroxybupropion, erythrohydroxybupropion, or threohydroxybupropion, for at least 60 days.

29. The method of claim 22, wherein about 40 mg to about 50 mg of dextromethorphan are administered per dose.