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 in need of treatment with 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 hydrobromide, or a molar equivalent amount of the free base form or another salt form of dextromethorphan, once a day or twice a day; and 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 1,000 times the AUC 0-24 that would result from administering 60 mg of dextromethorphan hydrobromide without 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 60 mg of dextromethorphan hydrobromide without the bupropion for eight consecutive days.
3 . 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 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 1,300 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 44 mg to about 46 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 75 mg/mL to 158 mg/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 the C min of dextromethorphan on the eighth day is about 50 mg/mL to 119 mg/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 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 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.