Compositions and Methods for Increasing the Metabolic Lifetime of Dextromethorphan and Related Pharmacodynamic Effects

• US 20160375012A1
• Filed: 09/12/2016
• Published: 12/29/2016
• Est. Priority Date: 11/05/2013
• Status: Active Grant

• Current Assignee: Antecip Bioventures II LLC
• Original Assignee: Antecip Bioventures II LLC
• Inventors: Tabuteau, Herriot
• Granted Patent: US 9,700,553 B2
• Time in Patent Office: Days
• 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 31/135 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 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 correcting extensive metabolism of the dextromethorphan in a human subject in need thereof, comprising co-administering to the human subject once a day for at least eight consecutive days or twice a day for at least eight consecutive days:

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

2) a dextromethorphan;

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 AUC_0-24 of the dextromethorphan that is at least about 50 ng·

hr/mL, and the first AUC_0-24 of the dextromethorphan is at least about 20 times a second AUC_0-24 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.

2. The method of claim 1, wherein the daily dose of the dextromethorphan is about 40 mg to about 200 mg.

3. The method of claim 1, wherein the daily dose of the dextromethorphan is about 40 mg to about 90 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 AUC_0-24 of the dextromethorphan is at least about 30 times the second AUC_0-24 of the dextromethorphan.

8. The method of claim 1, wherein the first AUC_0-24 of the dextromethorphan is at least about 40 times the second AUC_0-24 of the dextromethorphan.

9. The method of claim 5, wherein the first AUC_0-24 of the dextromethorphan is at least about 50 times the second AUC_0-24 of the dextromethorphan.

10. The method of claim 1, wherein the first AUC_0-24 of the dextromethorphan is at least about 100 ng·

hr/mL.

11. The method of claim 1, wherein the first AUC_0-24 of the dextromethorphan is at least about 200 ng·

hr/mL.

12. The method of claim 1, wherein the first AUC_0-24 of the dextromethorphan is at least about 400 ng·

hr/mL.

13. The method of claim 5, wherein the first AUC_0-24 of the dextromethorphan is at least about 600 ng·

hr/mL.

14. The method of claim 1, wherein the first AUC_0-24 of the dextromethorphan is at least about 800 ng·

hr/mL.

15. The method of claim 1, wherein the first AUC_0-24 of the dextromethorphan is at least about 1000 ng·

hr/mL.

16. The method of claim 1, wherein the daily dose of the bupropion is about 10 mg to about 300 mg.

17. The method of claim 1, wherein the daily dose of the bupropion is about 50 mg to about 220 mg.

18. The method of claim 1, wherein a single dose of the bupropion is about 60 mg to about 100 mg.

19. The method of claim 5, wherein a single dose of the bupropion is about 100 mg to about 140 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, the bupropion or the dextromethorphan.

28. 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.

29. 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.

30. 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.