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 enhancing dextromethorphan plasma levels in a human being, comprising co-administering a bupropion with a dextromethorphan, to the human being, for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein the weight ratio between the dextromethorphan and the bupropion is about 0.4 to about 0.7, and wherein, on the eighth day that the bupropion and the dextromethorphan are co-administered, the AUC 0-12 of dextromethorphan is at least about 15 times the AUC 0-12 of dextromethorphan that would result from administering the same amount of the dextromethorphan without the bupropion for eight consecutive days.
2. The method of claim 1 , wherein the bupropion and the dextromethorphan are co-administered once or twice daily for at least eight consecutive days.
3. The method of claim 1 , wherein the bupropion and the dextromethorphan are administered in a single dosage form.
4. The method of claim 3 , wherein the single dosage form is a solid.
5. The method of claim 3 , wherein the single dosage form is a liquid.
6. The method of claim 3 , wherein about 40 mg to about 300 mg of the dextromethorphan is administered in the single dosage form.
7. The method of claim 3 , wherein about 30 mg to about 120 mg of the bupropion is administered in the single dosage form.
8. The method of claim 1 , wherein the weight ratio between the dextromethorphan and the bupropion is about 0.4 to about 0.6.
9. The method of claim 1 , wherein the weight ratio between the dextromethorphan and the bupropion is about 0.4 to about 0.5.
10. The method of claim 1 , wherein the weight ratio between the dextromethorphan and the bupropion is about 0.4 to about 0.45.
11. The method of claim 1 , wherein the weight ratio between the dextromethorphan and the bupropion is about 0.42 to about 0.44.
12. The method of claim 1 , wherein the bupropion and the dextromethorphan are co-administered once daily for a first period of consecutive days and twice daily for a second period of consecutive days.
13. The method of claim 1 , wherein, on the eighth day that the bupropion and the dextromethorphan are co-administered, the AUC 0-12 of dextromethorphan is at least about 20 times the AUC 0-12 of dextromethorphan that would result from administering the same amount of the dextromethorphan without the bupropion for eight consecutive days.
14. The method of claim 1 , wherein the bupropion is not racemic.
15. The method of claim 14 , wherein the bupropion contains an enantiomeric excess of an R-enantiomer.
16. The method of claim 14 , wherein the bupropion contains an enantiomeric excess of an S-enantiomer.
17. A method of treating a human being in need of treatment with dextromethorphan, comprising administering a bupropion with a dextromethorphan to the human being for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan, wherein the bupropion is administered in an amount that results in a C avg of dextromethorphan on the eighth day of at least about 25 ng/mL, and wherein, on the eighth day that the bupropion and the dextromethorphan are co-administered, the AUC 0-12 of dextromethorphan is at least about 15 times the AUC 0-12 of dextromethorphan that would result from administering the same amount of the dextromethorphan without the bupropion for eight consecutive days.
18. The method of claim 17 , wherein between about 35 mg per day and about 100 mg per day of the dextromethorphan is administered.
19. The method of claim 17 , wherein between about 90 mg per day and about 225 mg per day of the bupropion is administered.
20. The method of claim 17 , wherein about 45 mg of the dextromethorphan is orally administered twice a day.
21. The method of claim 20 , wherein about 105 mg of the bupropion is orally administered twice a day.
22. The method of claim 17 , wherein about 105 mg of the bupropion is orally administered twice a day.
23. The method of claim 17 , wherein the C avg of dextromethorphan on the eighth day is at least about 30 ng/mL.
24. The method of claim 17 , wherein the C avg of dextromethorphan on the eighth day is at least about 50 ng/mL.
25. The method of claim 17 , wherein the C avg of dextromethorphan on the eighth day is at least about 100 ng/mL.
26. The method of claim 17 , wherein the bupropion and the dextromethorphan are administered in a single dosage form.
27. The method of claim 26 , where the single dosage form is administered once a day for a first period of consecutive days and twice a day for a second period of consecutive days.
28. The method of claim 17 , wherein the AUC 0-12 of dextromethorphan on the eighth day is between about 700 ng·hr/mL and about 1000 ng·hr/mL.
29. The method of claim 17 , wherein the C max of dextromethorphan on the eighth day is between about 70 ng/mL and about 100 ng/mL.