Bupropion as a modulator of drug activity
View Patent ↗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 administering for at least eight consecutive days a combination of dextromethorphan and bupropion to a human being, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein the combination is administered in a dosage form having properties effective for providing a C max of dextromethorphan on the eighth day of about 40 ng/mL to about 75 ng/mL, and wherein on the eighth day the combination is administered 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.
2. The method of claim 1 , wherein the dosage form is a single oral dosage form.
3. The method of claim 2 , wherein the single oral dosage form is a solid.
4. The method of claim 3 , wherein the single solid oral dosage form further comprises a binder, a disintegrating agent or a lubricant.
5. The method of claim 3 , wherein the single solid oral dosage form is a tablet, a troche, a pill, or a capsule.
6. The method of claim 2 , wherein the single oral dosage form is a liquid.
7. The method of claim 6 , wherein the single liquid dosage form comprises a liquid or a 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 C max of dextromethorphan on the eighth day is about 45 ng/mL to about 70 ng/mL.
11. The method of claim 1 , wherein the C max of dextromethorphan on the eighth day is about 50 ng/mL to about 60 ng/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 400 ng·hr/mL to about 700 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 450 ng·hr/mL to about 650 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 500 ng·hr/mL to about 600 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 550 ng·hr/mL to about 600 ng·hr/mL.
16. A method for treating a human being with dextromethorphan, comprising administering dextromethorphan and bupropion once or twice daily for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein dextromethorphan and bupropion are administered in amounts that result in an AUC 0-12 of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered that is about 400 ng·hr/mL to about 700 ng·hr/mL, and wherein the AUC 0-12 of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is at least about 20 times the AUC 0-12 of dextromethorphan that would result from administering the same amount of dextromethorphan without bupropion.
17. The method of claim 16 , wherein the AUC 0-12 of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is about 450 ng·hr/mL to about 650 ng·hr/mL.
18. The method of claim 16 , wherein the AUC 0-12 of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is about 500 ng·hr/mL to about 600 ng·hr/mL.
19. The method of claim 16 , wherein the AUC 0-12 of dextromethorphan on the eighth day that dextromethorphan and bupropion are administered is about 550 ng·hr/mL to about 600 ng·hr/mL.
20. The method of claim 16 , wherein the C max of dextromethorphan on the eighth day is about 45 ng/mL to about 70 ng/mL.
21. The method of claim 16 , wherein the C max of dextromethorphan on the eighth day is about 50 ng/mL to about 60 ng/mL.
22. The method of claim 16 , wherein bupropion and dextromethorphan are co-administered together 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 a solid phase dispersion of bupropion and dextromethorphan.
28. The method of claim 22 , wherein the single oral dosage form is effective for immediate release of dextromethorphan.
29. The method of claim 22 , wherein the single oral dosage form is effective for sustained release of bupropion.
30. The method of claim 16 , wherein the co-administration is effective for increasing dextromethorphan plasma levels in the human being.