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 tablet once daily by mouth for 3 days, and after 3 days, administering the tablet twice daily by mouth, to a human being in need thereof, wherein the tablet contains about 45 mg of a dextromethorphan salt and about 105 mg of a bupropion salt as the only active pharmaceutical ingredients in the tablet.
2. The method of claim 1 , wherein the dextromethorphan salt is dextromethorphan hydrobromide.
3. The method of claim 1 , wherein the bupropion salt is bupropion hydrochloride.
4. The method of claim 2 , wherein the bupropion salt is bupropion hydrochloride.
5. The method of claim 3 , wherein the tablet comprises a sustained release formulation of the bupropion hydrochloride and an immediate release formulation of the dextromethorphan salt.
6. The method of claim 4 , wherein the tablet comprises a sustained release formulation of the bupropion hydrochloride and an immediate release formulation of the dextromethorphan hydrobromide.
7. The method of claim 1 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean dextromethorphan C max in the extensive metabolizers of dextromethorphan is at least about 75 ng/mL, the mean dextromethorphan C min in the extensive metabolizers of dextromethorphan is at least about 45 ng/mL, and the mean dextromethorphan AUC 0-12 in the extensive metabolizers of dextromethorphan is at least about 750 ng·hr/mL.
8. The method of claim 4 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean dextromethorphan C max in the extensive metabolizers of dextromethorphan is at least about 75 ng/mL, the mean dextromethorphan C min in the extensive metabolizers of dextromethorphan is at least about 45 ng/mL, and the mean dextromethorphan AUC 0-12 in the extensive metabolizers of dextromethorphan is at least about 750 ng·hr/mL.
9. The method of claim 1 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean dextromethorphan C max in the extensive metabolizers of dextromethorphan is about 75 ng/mL to about 10,000 ng/mL, the mean dextromethorphan C min in the extensive metabolizers of dextromethorphan is about 45 ng/mL to about 10,000 ng/mL, and the mean dextromethorphan AUC 0-12 in the extensive metabolizers of dextromethorphan is about 750 ng·hr/mL to about 50,000 ng·hr/mL.
10. The method of claim 4 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean dextromethorphan C max in the extensive metabolizers of dextromethorphan is about 75 ng/mL to about 10,000 ng/mL, the mean dextromethorphan C min in the extensive metabolizers of dextromethorphan is about 45 ng/mL to about 10,000 ng/mL, and the mean dextromethorphan AUC 0-12 in the extensive metabolizers of dextromethorphan is about 750 ng·hr/mL to about 50,000 ng·hr/mL.
11. The method of claim 2 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean dextromethorphan C max in the extensive metabolizers of dextromethorphan is about 75 ng/mL, the mean dextromethorphan C min in the extensive metabolizers of dextromethorphan is about 45 ng/mL, and the mean dextromethorphan AUC 0-12 in the extensive metabolizers of dextromethorphan is about 750 ng·hr/mL.
12. The method of claim 3 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean dextromethorphan C max in the extensive metabolizers of dextromethorphan is about 75 ng/mL, the mean dextromethorphan C min in the extensive metabolizers of dextromethorphan is about 45 ng/mL, and the mean dextromethorphan AUC 0-12 in the extensive metabolizers of dextromethorphan is about 750 ng·hr/mL.
13. The method of claim 1 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean bupropion C max , in the extensive metabolizers of dextromethorphan is at least about 50 ng/mL and the mean bupropion AUC 0-12 in the extensive metabolizers of dextromethorphan is at least about 600 ng·hr/mL.
14. The method of claim 4 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean bupropion C max , in the extensive metabolizers of dextromethorphan is at least about 50 ng/mL and the mean bupropion AUC 0-12 in the extensive metabolizers of dextromethorphan is at least about 600 ng·hr/mL.
15. The method of claim 1 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean bupropion C max , in the extensive metabolizers of dextromethorphan is about 50 ng/mL to about 1,500 ng/mL and the mean bupropion AUC 0-12 in the extensive metabolizers of dextromethorphan is about 600 ng·hr/mL to about 15,000 ng·hr/mL.
16. The method of claim 4 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean bupropion C max , in the extensive metabolizers of dextromethorphan is about 50 ng/mL to about 1,500 ng/mL and the mean bupropion AUC 0-12 in the extensive metabolizers of dextromethorphan is about 600 ng·hr/mL to about 15,000 ng·hr/mL.
17. The method of claim 1 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean bupropion C max , in the extensive metabolizers of dextromethorphan is about 90 ng/mL.
18. The method of claim 4 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean bupropion C max , in the extensive metabolizers of dextromethorphan is about 90 ng/mL.
19. The method of claim 1 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean T max , of dextromethorphan is about 4 hours.
20. The method of claim 4 , wherein the tablet has a property that, when the tablet is administered to extensive metabolizers of dextromethorphan once daily by mouth for 3 days, and the tablet is administered twice daily after 3 days so that the tablet is administered for a total of 8 days, on the eighth day that the tablet is administered, the mean T max of dextromethorphan is about 4 hours.
21. The method of claim 1 , wherein the human being experiences an improvement of a depressive symptom after the tablet is administered.
22. The method of claim 21 , wherein the depressive symptom comprises sadness.
23. The method of claim 21 , wherein the depressive symptom comprises reduced sleep.
24. The method of claim 21 , wherein the depressive symptom comprises reduced appetite.
25. The method of claim 21 , wherein the depressive symptom comprises difficulty concentrating.
26. The method of claim 21 , wherein the depressive symptom comprises lassitude.
27. The method of claim 21 , wherein the depressive symptom comprises pessimism.