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 a non-poor metabolizer of dextromethorphan; wherein about 50 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 about 40 mg to about 60 mg of dextromethorphan in a salt form, or a molar equivalent amount of the free base form of dextromethorphan, once a day or twice a day; and wherein co-administering the bupropion and the dextromethorphan results in a C min of dextromethorphan on the eighth day that is about 20 times to about 150 times the C min of dextromethorphan that results after the first dose of the bupropion and the dextromethorphan are co-administered.
2. The method of claim 1 , wherein co-administering the bupropion and the dextromethorphan results in a C min of dextromethorphan on the eighth day that is about 20 times to about 48 times the C min of dextromethorphan that results after the first dose of the bupropion and the dextromethorphan are co-administered.
3. The method of claim 1 , wherein co-administering the bupropion and the dextromethorphan results in a C min of dextromethorphan on the eighth day that is about 40 times the C min of dextromethorphan that results after the first dose of the bupropion and the dextromethorphan are co-administered.
4. The method of claim 2 , wherein about 70 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 in a salt form, or a molar equivalent amount of the free base form of dextromethorphan, once a day or twice a day to the human being.
5. The method of claim 4 , wherein the AUC 0-12 of dextromethorphan in the human being on the eighth day is about 750 ng·hr/mL.
6. The method of claim 4 , wherein the AUC 0-12 of dextromethorphan in the human being on the eighth day is about 700 ng·hr/mL to about 1686 ng·hr/mL.
7. The method of claim 6 , 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 44 mg to about 46 mg of dextromethorphan in a salt form, or a molar equivalent amount of the free base form of dextromethorphan, once a day or twice a day to the human being.
8. The method of claim 6 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of depression.
9. The method of claim 6 , wherein the C max of dextromethorphan in the human being on the eighth day is about 70 ng/mL to about 158 ng/mL.
10. The method of claim 9 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of depression.
11. The method of claim 6 , wherein the C min of dextromethorphan in the human being on the eighth day is about 40 ng/mL to about 119 ng/mL.
12. The method of claim 11 , wherein the bupropion and the dextromethorphan are co-administered to the human being for the treatment of depression.
13. The method of claim 11 , wherein the bupropion and the dextromethorphan are co-administered once a day or twice a day to the human being for at least 14 consecutive days.
14. The method of claim 11 , wherein the bupropion and the dextromethorphan are co-administered once a day or twice a day to the human being for at least 30 consecutive days.
15. The method of claim 11 , wherein the human being is converted to poor metabolizer status on the eighth day after co-administering the bupropion and the dextromethorphan.