Compositions and methods comprising bupropion or related compounds for sustained delivery of dextromethorphan
Dosage forms, drug delivery systems, and methods related to sustained release of dextromethorphan or improved therapeutic effects are disclosed. Typically, bupropion or a related compound is orally administered to a human being to be treated with, or being treated with, dextromethorphan.
1. A method, comprising treating a human being with dextromethorphan by administering once daily or twice daily for at least eight consecutive days a single dosage form comprising both dextromethorphan and bupropion to the human being, wherein the human being is an extensive metabolizer of dextromethorphan, wherein the dosage form contains about 40 mg to about 100 mg of dextromethorphan and the weight ratio of dextromethorphan to bupropion is about 0.2 to about 1.0, and wherein after eight consecutive days of administering the dosage form once daily or twice daily, the method results in an AUC 0-12 of dextromethorphan that is: 1) at least about 500 ng·hr/mL and 2) at least 15 times the AUC 0-12 of dextromethorphan that would be achieved by administering the same amount of dextromethorphan once daily or twice daily without bupropion for eight consecutive days.
2. The method of claim 1 , wherein the dosage form is an oral dosage form.
3. The method of claim 1 , wherein the dosage form is a solid dosage form that further comprises a binder.
4. The method of claim 1 , wherein the dosage form is a solid dosage form that further comprises a disintegrating agent.
5. The method of claim 1 , wherein the dosage form is a solid dosage form that further comprises a lubricant.
6. The method of claim 1 , wherein the dosage form comprises a liquid or solid phase dispersion of bupropion and dextromethorphan.
7. The method of claim 1 , wherein the dosage form is effective for immediate release of dextromethorphan.
8. The method of claim 1 , wherein the dosage form is effective for sustained release of bupropion.
9. The method of claim 1 , wherein after eight consecutive days of administering the dosage form once daily or twice daily, the AUC 0-12 of dextromethorphan is about 500 ng·hr/mL to about 600 ng·hr/mL.
10. The method of claim 1 , wherein after eight consecutive days of administering the dosage form once daily or twice daily, the AUC 0-12 of dextromethorphan is about 800 ng·hr/mL to about 900 ng·hr/mL.
11. The method of claim 1 , wherein after eight consecutive days of administering the dosage form once daily or twice daily, the AUC 0-12 of dextromethorphan is at least about 20 times the AUC 0-12 of dextromethorphan that would be achieved by administering the same amount of dextromethorphan once daily or twice daily without bupropion for eight consecutive days.
12. The method of claim 1 , wherein the once daily or twice daily administration of the dosage form results in a total daily dose of bupropion that is about 150 mg to about 200 mg.
13. The method of claim 1 , wherein the once daily or twice daily administration of the dosage form results in a total daily dose of bupropion that is about 200 mg to about 250 mg.
14. The method of claim 1 , wherein the once daily or twice daily administration of the dosage form results in a total daily dose of bupropion that is about 250 mg to about 300 mg.
15. The method of claim 1 , wherein the once daily or twice daily administration of the dosage form results in a total daily dose of dextromethorphan that is about 60 mg to about 100 mg.
16. A method for treating a human being with dextromethorphan, comprising administering to the human being a combination of dextromethorphan and bupropion in a single dosage form once daily or twice daily for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan, wherein the dosage form contains about 40 mg to about 100 mg of dextromethorphan and the weight ratio of dextromethorphan to bupropion is about 0.2 to about 1.0, and wherein, after the combination is administered once daily or twice daily for eight consecutive days: 1) the human being has a C max of dextromethorphan that is at least about 40 ng/mL and 2) the C max of dextromethorphan is at least about 15 times the C max of dextromethorphan that would result from administering the same amount of dextromethorphan once daily or twice daily without bupropion for eight consecutive days.
17. The method of claim 16 , wherein the C max of dextromethorphan on the eighth day that the combination is administered is at least about 20 times the C max of dextromethorphan that would result from administering the same amount of dextromethorphan once daily or twice daily without bupropion for eight consecutive days.
18. The method of claim 16 , wherein the C max of dextromethorphan on the eighth day that the combination is administered is about 50 ng/mL to about 60 ng/mL.
19. The method of claim 16 , wherein the C max of dextromethorphan on the eighth day that the combination is administered is about 80 ng/mL to about 90 ng/mL.
20. The method of claim 16 , wherein the single dosage form containing the combination is an oral dosage form.
21. The method of claim 16 , wherein the single dosage form containing the combination is a solid oral dosage form that further comprises a binder.
22. The method of claim 16 , wherein the single dosage form containing the combination is a solid oral dosage form that further comprises a disintegrating agent.
23. The method of claim 16 , wherein the single dosage form containing the combination is a solid oral dosage form that further comprises a lubricant.
24. The method of claim 16 , wherein the single dosage form containing the combination is a solid oral dosage form that is effective for immediate release of dextromethorphan and sustained release of bupropion.
25. The method of claim 20 , wherein the once daily or twice daily administration of the combination results in a total daily dose of bupropion that is about 200 mg to about 250 mg.
26. The method of claim 20 , wherein the once daily or twice daily administration of the combination results in a total daily dose of dextromethorphan that is about 60 mg to about 100 mg.