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 for treating a human being with dextromethorphan comprising administering once or twice daily for at least eight consecutive days a combination of dextromethorphan and bupropion to the human being, wherein the human being is an extensive metabolizer of dextromethorphan and in need of treatment with dextromethorphan, wherein the combination is administered in a dosage form, which provides an AUC 0-12 of dextromethorphan of about 700 ng·hr/mL to about 1050 ng·hr/mL for the human being after eight consecutive days of administering the dosage form comprising the combination, and wherein after eight consecutive days of administering the dosage form comprising the combination to the human being, the AUC 0-12 of dextromethorphan is at least about 15 times the AUC 0-12 of dextromethorphan that would be achieved by administering the same amount of dextromethorphan 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 2 , wherein the oral dosage form is a solid.
4. The method of claim 3 , wherein the solid oral dosage form further comprises a binder, a disintegrating agent or a lubricant.
5. The method of claim 3 , wherein the solid oral dosage form is a tablet, a troche, a pill or a capsule.
6. The method of claim 2 , wherein the oral dosage form is a liquid.
7. The method of claim 6 , wherein the liquid dosage form comprises a liquid or solid phase dispersion of bupropion and dextromethorphan.
8. The method of claim 1 , wherein the dosage form is effective for immediate release of dextromethorphan.
9. The method of claim 1 , wherein the dosage form is effective for sustained release of bupropion.
10. The method of claim 1 , wherein the AUC 0-12 of dextromethorphan on the eighth day that the combination is administered is about 750 ng·hr/mL to about 1000 ng·hr/mL.
11. The method of claim 1 , wherein the AUC 0-12 of dextromethorphan on the eighth day that the combination is administered is about 800 ng·hr/mL to about 950 ng·hr/mL.
12. The method of claim 1 , wherein the AUC 0-12 of dextromethorphan on the eighth day that the combination is administered is about 850 ng·hr/mL to about 900 ng·hr/mL.
13. The method of claim 1 , wherein the AUC 0-12 of dextromethorphan on the eighth day that the combination is administered is about 800 ng·hr/mL to about 900 ng·hr/mL.
14. The method of claim 1 , wherein the AUC 0-12 of dextromethorphan on the eighth day that the combination is administered is about 850 ng·hr/mL to about 950 ng·hr/mL.
15. The method of claim 1 , wherein the AUC 0-12 of dextromethorphan on the eighth day that the combination is administered is about 750 ng·hr/mL to about 950 ng·hr/mL.
16. The method of claim 1 , wherein on the eighth day the combination is administered 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 without bupropion for eight consecutive days.
17. A method for treating a human being with dextromethorphan, comprising administering to the human being dextromethorphan in combination with bupropion once or twice daily for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan and in need of treatment with dextromethorphan, wherein dextromethorphan and bupropion are administered in a dosage form, which provides a C max of dextromethorphan of about 60 ng/mL to about 110 ng/mL for the human being after eight consecutive days of administering the dosage form, and wherein after eight consecutive days of administering the dosage form to the human being, the C max of dextromethorphan is at least about 15 times the C max of dextromethorphan that would be achieved by administering the same amount of dextromethorphan without bupropion for eight consecutive days.
18. The method of claim 17 , wherein the C max of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is at least about 20 times the C max of dextromethorphan that would result from administering the same amount of dextromethorphan without bupropion.
19. The method of claim 17 , wherein the C max of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is about 65 ng/mL to about 105 ng/mL.
20. The method of claim 17 , wherein the C max of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is about 70 ng/mL to about 100 ng/mL.
21. The method of claim 17 , wherein the C max of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is about 75 ng/mL to about 95 ng/mL.
22. The method of claim 17 , wherein the C max of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is about 80 ng/mL to about 90 ng/mL.
23. The method of claim 17 , wherein the C max of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is about 75 ng/mL to about 90 ng/mL.
24. The method of claim 17 , wherein the C max of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is about 80 ng/mL to about 95 ng/mL.
25. The method of claim 17 , wherein the dosage form is an oral dosage form.
26. The method of claim 25 , wherein the oral dosage form is a solid in the form of a tablet, a troche, a pill or a capsule.
27. The method of claim 26 , wherein the solid oral dosage form further comprises a binder, a disintegrating agent or a lubricant.
28. The method of claim 25 , wherein the oral dosage form is a liquid and comprises a liquid or solid phase dispersion of bupropion and dextromethorphan.
29. The method of claim 25 , wherein the oral dosage form is effective for immediate release of dextromethorphan and sustained release of bupropion.