Bupropion as a modulator of drug activity

Abstract

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.

What is claimed is: 
     
         1 . A method of reducing a risk of seizure associated with use of bupropion to treat depression, comprising orally administering a dextromethorphan-bupropion combination twice a day for at least 23 days, to a human being suffering from depression, wherein the dextromethorphan-bupropion combination comprises about 0.3 mg/kg to about 0.9 mg/kg of a dextromethorphan and about 90 mg to about 115 mg of a bupropion, wherein the method is: 1) at least as effective in treating depression, and 2) reduces the risk of seizure to the human being, as compared to orally administering 150 mg of the bupropion alone twice a day to the human being for the same number of days. 
     
     
         2 . The method of  claim 1 , further comprising orally administering the dextromethorphan-bupropion combination once a day for 1, 2, 3, 4, 5, 6, or 7 days, prior to orally administering the dextromethorphan-bupropion combination twice a day for at least 23 days. 
     
     
         3 . The method of  claim 1 , wherein the dextromethorphan-bupropion combination comprises about 0.75 mg/kg of the dextromethorphan. 
     
     
         4 . The method of  claim 3 , wherein dextromethorphan-bupropion combination is orally administered once a day for 1, 2, 3, 4, 5, 6, or 7 days prior to orally administering the dextromethorphan-bupropion combination twice a day for at least 23 days. 
     
     
         5 . The method of  claim 1 , wherein the dextromethorphan-bupropion combination comprises about 100 mg to about 110 mg of the bupropion. 
     
     
         6 . The method of  claim 1 , wherein the dextromethorphan-bupropion combination comprises about 105 mg of the bupropion. 
     
     
         7 . The method of  claim 5 , wherein the dextromethorphan-bupropion combination comprises about 105 mg of the bupropion. 
     
     
         8 . The method of  claim 1 , wherein the dextromethorphan is orally administered in a dosage form that is immediate release for the dextromethorphan and the bupropion is administered in a dosage form that is sustained release for the bupropion. 
     
     
         9 . The method of  claim 1 , wherein the dextromethorphan-bupropion combination is more effective than orally administering 150 mg of the bupropion alone twice a day to the human being. 
     
     
         10 . The method of  claim 1 , wherein the bupropion contains an enantiomeric excess of an enantiomer. 
     
     
         11 . The method of  claim 10 , wherein the bupropion comprises an enantiomeric excess of an R-enantiomer. 
     
     
         12 . The method of  claim 10 , wherein the bupropion comprises an enantiomeric excess of an S-enantiomer. 
     
     
         13 . The method of  claim 1 , wherein the dextromethorphan comprises a deuterium-modified dextromethorphan. 
     
     
         14 . A method of improving the therapeutic effect of bupropion in treating depression, comprising orally co-administering about 40 mg to about 55 mg of a dextromethorphan with about 100 mg to about 110 mg of a bupropion, twice a day for at least five weeks, to a human being suffering from depression, wherein the method is more effective than treating the depression of that human being by orally administering 150 mg of the bupropion alone twice a day to the human being for five weeks. 
     
     
         15 . The method of  claim 14 , wherein about 45 mg of the dextromethorphan is orally administered twice a day. 
     
     
         16 . The method of  claim 14 , wherein about 105 mg of the bupropion is orally administered twice a day. 
     
     
         17 . The method of  claim 15 , wherein about 105 mg of the bupropion is orally administered twice a day. 
     
     
         18 . The method of  claim 17 , wherein about 45 mg of the dextromethorphan and about 105 mg of the bupropion are administered twice a day for at least 12 weeks. 
     
     
         19 . The method of  claim 18 , wherein about 45 mg of the dextromethorphan and about 105 mg of the bupropion are present together in a single dosage form that is administered twice a day. 
     
     
         20 . The method of  claim 19 , wherein the dextromethorphan is formulated for immediate release and the bupropion is formulated for extended release. 
     
     
         21 . The method of  claim 14 , further comprising orally co-administering about 40 mg to about 55 mg of the dextromethorphan with about 100 mg to about 110 mg of the bupropion once a day for 1, 2, 3, 4, 5, 6, or 7 days, prior to orally co-administering about 40 mg to about 55 mg of the dextromethorphan with about 100 mg to about 110 mg of the bupropion twice a day for at least five weeks. 
     
     
         22 . The method of  claim 7 , further comprising orally co-administering about 45 mg of the dextromethorphan with about 105 mg of the bupropion once a day for about 1 to 7 days, prior to orally co-administering about 45 mg of the dextromethorphan with about 105 mg of the bupropion twice a day for at least five weeks. 
     
     
         23 . The method of  claim 14 , wherein the bupropion is not a racemic mixture. 
     
     
         24 . The method of  claim 23 , wherein the bupropion contains an enantiomeric excess of an R-enantiomer. 
     
     
         25 . The method of  claim 23 , wherein the bupropion contains an enantiomeric excess of an S-enantiomer. 
     
     
         26 . The method of  claim 14 , wherein the dextromethorphan comprises a deuterium-modified dextromethorphan. 
     
     
         27 . The method of  claim 14 , wherein the human being is suffering from treatment-resistant depression. 
     
     
         28 . The method of  claim 14 , wherein the human being is at least 18 years of age. 
     
     
         29 . The method of  claim 22 , wherein the dextromethorphan and the bupropion are administered in a single dosage form.