Bupropion as a modulator of drug activity
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 of treating major depressive disorder, comprising administering a dosage form by mouth once daily or twice daily to a human patient in need thereof, wherein the dosage form comprises about 105 mg of bupropion hydrochloride and about 45 mg of a dextromethorphan salt as the only therapeutically active compounds in the dosage form, wherein the human patient does not experience an adverse event as a result of receiving the dosage form, and wherein the adverse event is constipation.
2. The method of claim 1 , wherein the dosage form is a tablet.
3. The method of claim 1 , wherein bupropion hydrochloride is in a sustained release formulation.
4. The method of claim 3 , wherein the dextromethorphan salt is in an immediate release formulation.
5. The method of claim 1 , wherein the dosage form is administered once daily by mouth for three days followed by twice daily by mouth thereafter for a total of at least 8 days, and wherein on the eighth day that the dosage form is administered, the C max of bupropion in the human patient is about 9×10 1 ng/mL.
6. The method of claim 1 , wherein the dosage form is administered once daily by mouth for three days followed by twice daily by mouth thereafter for a total of at least 8 days, and wherein on the eighth day that the dosage form is administered, the AUC 0-12 of bupropion in the human patient is about 7×10 2 ng·hr/mL.
7. The method of claim 1 , wherein the dextromethorphan salt is dextromethorphan hydrobromide.
8. The method of claim 7 , wherein the dosage form is a tablet.
9. The method of claim 7 , wherein bupropion hydrochloride is in a sustained release formulation.
10. The method of claim 9 , wherein dextromethorphan hydrobromide is in an immediate release formulation.
11. The method of claim 7 , wherein the dosage form is administered once daily by mouth for three days followed by twice daily by mouth thereafter for a total of at least 8 days, and wherein on the eighth day that the dosage form is administered, the C max of bupropion in the human patient is about 9×10 1 ng/mL.
12. The method of claim 7 , wherein the dosage form is administered once daily by mouth for three days followed by twice daily by mouth thereafter for a total of at least 8 days, and wherein on the eighth day that the dosage form is administered, the AUC 0-12 of bupropion in the human patient is about 7×10 2 ng·hr/mL.
13. The method of claim 7 , wherein the human patient is an extensive CYP2D6 metabolizer.
14. The method of claim 13 , wherein the dosage form is administered once daily by mouth for three days followed by twice daily by mouth thereafter.
15. The method of claim 1 , wherein the human patient is an extensive CYP2D6 metabolizer.
16. The method of claim 15 , wherein the dosage form is a tablet.
17. The method of claim 15 , wherein bupropion hydrochloride is in a sustained release formulation.
18. The method of claim 17 , wherein the dextromethorphan salt is in an immediate release formulation.
19. The method of claim 15 , wherein the dosage form is administered once daily by mouth for three days followed by twice daily by mouth thereafter for a total of at least 8 days, and wherein on the eighth day that the dosage form is administered, the C max of bupropion in the human patient is about 9×10 1 ng/mL.
20. The method of claim 15 , wherein the dosage form is administered once daily by mouth for three days followed by twice daily by mouth thereafter for a total of at least 8 days, and wherein on the eighth day that the dosage form is administered, the AUC 0-12 of bupropion in the human patient is about 7×10 2 ng·hr/mL.
21. The method of claim 1 , wherein the dosage form is administered once daily by mouth for three days followed by twice daily by mouth thereafter.
22. The method of claim 21 , wherein the human patient is an extensive CYP2D6 metabolizer.
23. The method of claim 21 , wherein the dosage form is a tablet.
24. The method of claim 21 , wherein bupropion hydrochloride is in a sustained release formulation.
25. The method of claim 24 , wherein the dextromethorphan salt is in an immediate release formulation.
26. The method of claim 23 , wherein the dosage form is administered for a total of at least 8 days, and wherein on the eighth day that the dosage form is administered, the C max of bupropion in the human patient is about 9×10 1 ng/mL.
27. The method of claim 23 , wherein the dosage form is administered for a total of at least 8 days, and wherein on the eighth day that the dosage form is administered, the AUC 0-12 of bupropion in the human patient is about 7×10 2 ng·hr/mL.
28. A method of treating major depressive disorder, comprising administering a dosage form by mouth once daily or twice daily to a human patient in need thereof, wherein the dosage form consists essentially of about 105 mg of bupropion hydrochloride and about 45 mg of a dextromethorphan salt, wherein the human patient does not experience an adverse event as a result of receiving the dosage form, and wherein the adverse event is constipation.
29. A method of treating major depressive disorder, comprising orally administering to a human patient in need thereof once daily or twice daily a dosage form comprising therapeutically active compounds, wherein the therapeutically active compounds in the dosage form consist of (i) about 105 mg of bupropion hydrochloride and (ii) about 45 mg of a dextromethorphan salt, wherein the human patient does not experience an adverse event as a result of receiving the dosage form, and wherein the adverse event is constipation.