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