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 increasing dextromethorphan plasma levels, comprising co-administering bupropion and dextromethorphan once a day or twice a day for at least 8 consecutive days to a human being who is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan; wherein about 90 mg to about 220 mg of bupropion hydrochloride, or a molar equivalent amount of the free base form or another salt form of bupropion is co-administered with dextromethorphan hydrobromide, or the free base form or another salt form of dextromethorphan, once or twice a day; and wherein the bupropion and the dextromethorphan are the only therapeutically active agents to be co-administered and co-administering the bupropion and the dextromethorphan results in an AUC 0-24 of dextromethorphan on the eighth day that is at least about 20 times the AUC 0-24 of dextromethorphan that would result from administering the same daily dose of the dextromethorphan without the bupropion for eight consecutive days.
2. The method of claim 1 , wherein co-administering the bupropion and the dextromethorphan results in an AUC 0-24 of dextromethorphan on the eighth day that is about 20 times to about 80 times the AUC 0-24 that would result from administering the same daily dose of the dextromethorphan without the bupropion for eight consecutive days.
3. The method of claim 2 , wherein about 90 mg to about 150 mg of bupropion hydrochloride, or a molar equivalent amount of the free base form or another salt form of bupropion, is co-administered with about 40 mg to about 60 mg of dextromethorphan hydrobromide, or a molar equivalent amount of the free base form or another salt form of dextromethorphan, once a day or twice a day.
4. The method of claim 3 , wherein the AUC 0-24 of dextromethorphan on the eighth day is about 1,900 ng·hr/mL.
5. The method of claim 3 , wherein the AUC 0-24 of dextromethorphan on the eighth day is about 1300 ng·hr/mL to 2,975 ng·hr/mL.
6. The method of claim 5 , wherein about 105 mg of bupropion hydrochloride, or a molar equivalent amount of the free base form or another salt form of bupropion, is co-administered with about 42 mg to about 48 mg of dextromethorphan hydrobromide, or a molar equivalent amount of the free base form or another salt form of dextromethorphan, once a day or twice a day.
7. The method of claim 5 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of depression.
8. The method of claim 5 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of nicotine addiction.
9. The method of claim 5 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of agitation associated with Alzheimer's disease.
10. The method of claim 5 , wherein the C max of dextromethorphan on the eighth day is about 69 ng/mL to about 154 ng/ml.
11. The method of claim 10 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of depression.
12. The method of claim 10 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of nicotine addiction.
13. The method of claim 10 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of agitation associated with Alzheimer's disease.
14. The method of claim 10 , wherein AUC 0-12 of bupropion on the eighth day is at least 600 ng·hr/mL.
15. The method of claim 14 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of depression.
16. The method of claim 14 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of nicotine addiction.
17. The method of claim 14 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of agitation associated with Alzheimer's disease.
18. The method of claim 14 , wherein the bupropion and the dextromethorphan are co-administered once a day or twice a day for at least 14 consecutive days.
19. The method of claim 14 , wherein the bupropion and the dextromethorphan are co-administered once a day or twice a day for at least 30 consecutive days.
20. The method of claim 14 , wherein the human being is converted to poor metabolizer status on the eighth day after co-administering the bupropion and the dextromethorphan.