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 extending dextromethorphan plasma levels in a human being that is an extensive metabolizer of dextromethorphan and is in need of treatment with dextromethorphan, comprising co-administering: 1) a hydroxybupropion, a threohydroxybupropion, an erythrohydroxybupropion, or a bupropion with 2) a dextromethorphan, to the human being once or twice a day for at least eight consecutive days, wherein the daily dose of the dextromethorphan is about 15 mg to about 300 mg, and co-administering the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion with the dextromethorphan results in a C avg of the dextromethorphan that, on the eighth day, is at least about 20 times the C avg that would be achieved by administering the same amount of the dextromethorphan without the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion for eight consecutive days.
2. The method of claim 1 , wherein the daily dose of the dextromethorphan is about 20 mg to about 250 mg.
3. The method of claim 1 , wherein the daily dose of the dextromethorphan is about 30 mg to about 200 mg.
4. The method of claim 1 , wherein the daily dose of the dextromethorphan is about 40 mg to about 150 mg.
5. The method of claim 1 , wherein the dextromethorphan is co-administered in a dosage form that contains about 40 mg to about 50 mg of the dextromethorphan.
6. The method of claim 4 , wherein the dextromethorphan is co-administered in a dosage form that contains about 40 mg to about 50 mg of the dextromethorphan.
7. The method of claim 1 , wherein the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion and the dextromethorphan are co-administered together in a single, solid oral dosage form.
8. The method of claim 7 , wherein the single solid oral dosage form further comprises a binder, a disintegrating agent, or a lubricant.
9. The method of claim 1 , further comprising co-administering the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion with the dextromethorphan to the human being once or twice a day for at least 14 consecutive days.
10. The method of claim 1 , further comprising co-administering the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion with the dextromethorphan to the human being once or twice a day for at least 30 consecutive days.
11. The method of claim 1 , comprising co-administering the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion with the dextromethorphan to the human being twice a day.
12. The method of claim 1 , wherein, on the eighth day, the C avg of the dextromethorphan is at least about 10 ng·hr/mL.
13. The method of claim 1 , wherein, on the eighth day, the C avg of the dextromethorphan is at least about 100 ng·hr/mL.
14. The method of claim 1 , wherein the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, the bupropion, or the dextromethorphan is deuterium-modified.
15. The method of claim 14 , wherein the dextromethorphan is deuterium-modified.
16. A method of extending dextromethorphan plasma levels in a human being that is an extensive metabolizer of dextromethorphan and is in need of treatment with dextromethorphan, comprising co-administering: 1) a hydroxybupropion, a threohydroxybupropion, an erythrohydroxybupropion, or a bupropion with 2) a dextromethorphan, to the human being once or twice a day for at least eight consecutive days, wherein the daily dose of the dextromethorphan is about 20 mg to about 250 mg, and co-administering the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion with the dextromethorphan results in a C avg of the dextromethorphan that, on the eighth day, is at least about 15 times the C avg that would be achieved by administering the same amount of the dextromethorphan without the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion for eight consecutive days.
17. The method of claim 16 , wherein the dextromethorphan is deuterium-modified.
18. The method of claim 16 , wherein the daily dose of the dextromethorphan is about 30 mg to about 150 mg.
19. The method of claim 16 , wherein the dextromethorphan is co-administered in a dosage form that contains about 40 mg to about 50 mg of the dextromethorphan.
20. The method of claim 16 , wherein the dextromethorphan with the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion is co-administered in an oral dosage form.
21. The method of claim 20 , wherein the oral dosage form is solid.
22. A method of extending dextromethorphan plasma levels in a human being that is an extensive metabolizer of dextromethorphan and is in need of treatment with dextromethorphan, comprising co-administering: 1) a hydroxybupropion, a threohydroxybupropion, an erythrohydroxybupropion, or a bupropion with 2) a dextromethorphan, to the human being once or twice a day for at least eight consecutive days, wherein the daily dose of the dextromethorphan is about 50 mg to about 400 mg, and co-administering the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion with the dextromethorphan results in a C avg of the dextromethorphan that, on the eighth day, is at least about 15 times the C avg that would be achieved by administering the same amount of the dextromethorphan without the hydroxybupropion, the threohydroxybupropion, the erythrohydroxybupropion, or the bupropion for eight consecutive days.
23. The method of claim 22 , wherein the dextromethorphan is co-administered with the hydroxybupropion or the bupropion.
24. The method of claim 22 , wherein the dextromethorphan is co-administered with the threohydroxybupropion or the bupropion.
25. The method of claim 22 , wherein the dextromethorphan is co-administered with the erythrohydroxybupropion or the bupropion.