Bupropion as 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 to a human being in need thereof, wherein the tablet is administered to the human being once daily by mouth for 3 days, and after 3 days the tablet is administered twice daily by mouth so that the tablet is administered to the human being for at least 8 days, 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, wherein the tablet comprises a sustained release formulation of the bupropion salt and an immediate release formulation of the dextromethorphan salt, and the tablet is formulated so that on the eighth day that the tablet is administered, the T max of dextromethorphan in the human being is about 4 hours.
2. The method of claim 1 , wherein the tablet is formulated so that on the eighth day that the tablet is administered, the C max of hydroxybupropion is about 1,000 ng/mL.
3. The method of claim 1 , wherein the tablet is formulated so that on the eighth day that the tablet is administered, the C max of hydroxybupropion is about 1,000 ng/mL to about 10,000 ng/mL.
4. The method of claim 1 , wherein the tablet is formulated so that on the eighth day that the tablet is administered, the AUC 0-12 of hydroxybupropion is about 10,000 ng·hr/mL.
5. The method of claim 1 , wherein the tablet is formulated so that on the eighth day that the tablet is administered, the AUC 0-12 of hydroxybupropion is about 10,000 ng·hr/mL to about 50,000 ng·hr/mL.
6. The method of claim 1 , wherein the dextromethorphan salt is dextromethorphan hydrobromide.
7. The method of claim 1 , wherein the bupropion salt is bupropion hydrochloride.
8. The method of claim 6 , wherein the bupropion salt is bupropion hydrochloride.
9. The method of claim 1 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean dextromethorphan C max is at least about 75 ng/mL, the mean dextromethorphan C min is at least about 45 ng/mL, and the mean dextromethorphan AUC 0-12 is at least about 750 ng·hr/mL.
10. The method of claim 8 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean dextromethorphan C max is at least about 75 ng/mL, the mean dextromethorphan C min is at least about 45 ng/mL, and the mean dextromethorphan AUC 0-12 is at least about 750 ng·hr/mL.
11. The method of claim 1 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean dextromethorphan C max is about 75 ng/mL to about 10,000 ng/mL, the mean dextromethorphan C min is about 45 ng/mL to about 10,000 ng/mL, and the mean dextromethorphan AUC 0-12 is about 750 ng·hr/mL to about 50,000 ng·hr/mL.
12. The method of claim 8 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean dextromethorphan C max is about 75 ng/mL to about 10,000 ng/mL, the mean dextromethorphan C min is about 45 ng/mL to about 10,000 ng/mL, and the mean dextromethorphan AUC 0-12 is about 750 ng·hr/mL to about 50,000 ng·hr/mL.
13. The method of claim 6 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean dextromethorphan C max is about 75 ng/mL, the mean dextromethorphan C min is about 45 ng/mL, and the mean dextromethorphan AUC 0-12 is about 750 ng·hr/mL.
14. The method of claim 7 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean dextromethorphan C max is about 75 ng/mL, the mean dextromethorphan C min is about 45 ng/mL, and the mean dextromethorphan AUC 0-12 is about 750 ng·hr/mL.
15. The method of claim 1 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean bupropion C max is at least about 50 ng/mL and the mean bupropion AUC 0-12 is at least about 600 ng·hr/mL.
16. The method of claim 8 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean bupropion C max is at least about 50 ng/mL and the mean bupropion AUC 0-12 is at least about 600 ng·hr/mL.
17. The method of claim 1 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean bupropion C max is about 50 ng/mL to about 1,500 ng/mL and the mean bupropion AUC 0-12 is about 600 ng·hr/mL to about 15,000 ng·hr/mL.
18. The method of claim 8 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean bupropion C max is about 50 ng/mL to about 1,500 ng/mL and the mean bupropion AUC 0-12 is about 600 ng·hr/mL to about 15,000 ng·hr/mL.
19. The method of claim 1 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean bupropion C max is about 90 ng/mL.
20. The method of claim 8 , wherein the tablet is formulated so that, on the eighth day that the tablet is administered, the mean bupropion C max is about 90 ng/mL.
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.