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 increasing dextromethorphan plasma levels comprising:
 administering a dosage form for at least eight consecutive days to a human being that is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein the dosage form comprises a bupropion, a hydroxybupropion, a threohydroxybupropion, or an erythrohydroxybupropion, a pharmaceutically acceptable excipient, and a dextromethorphan;   wherein, on the eighth day of the administration of the dosage form the AUC 0-24  of dextromethorphan is at least about 100 ng·hr/mL, and is at least about 30 times the AUC 0-12  of dextromethorphan that would be achieved after administering the same amount of the dextromethorphan without co-administering the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion.   
     
     
         2 . The method of  claim 1 , wherein the dosage form comprises bupropion. 
     
     
         3 . The method of  claim 2 , wherein the human being receives about 50 mg to about 150 mg of the dextromethorphan per day. 
     
     
         4 . The method of  claim 1 , wherein the dosage form is solid. 
     
     
         5 . The method of  claim 1 , wherein the dosage form is a tablet, a troche, a pill, or a capsule. 
     
     
         6 . The method of  claim 1 , wherein the dosage form is administered twice a day. 
     
     
         7 . A method of preparing a dosage form for increasing dextromethorphan plasma levels comprising:
 mixing a bupropion, a hydroxybupropion, a threohydroxybupropion, or a erythrohydroxybupropion and a pharmaceutically acceptable excipient to form more than one unit of the dosage form;   wherein a sufficient number of units of the dosage form are packaged together to allow administration of a single unit of the dosage form once or twice a day for at least eight consecutive days;   wherein the dosage form is made available to a human being who is selected for being an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan who will receive the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, with a dextromethorphan for at least eight consecutive days; and   wherein the dosage form contains an amount of the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion such that eight consecutive days of co-administration of the dosage form with the dextromethorphan, to a human being that is an extensive metabolizer of dextromethorphan, results in a plasma level of dextromethorphan in the human being that is at least about 20 times the plasma level of dextromethorphan that would be achieved after administering the same amount of the dextromethorphan without co-administering the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion.   
     
     
         8 . The method of  claim 7 , wherein the dosage form comprises the bupropion. 
     
     
         9 . The method of  claim 7 , wherein the dosage form comprises the hydroxybupropion. 
     
     
         10 . The method of  claim 7 , wherein the dosage form comprises the threohydroxybupropion. 
     
     
         11 . The method of  claim 7 , wherein the dosage form comprises the erythrohydroxybupropion. 
     
     
         12 . The method of  claim 7 , wherein the dosage form contains, or is made available to the human being to be administered with, about 10 mg to about 500 mg dextromethorphan per day. 
     
     
         13 . The method of  claim 7 , wherein the dosage form contains, or is made available to the human being to be administered with, about 40 mg to about 50 mg dextromethorphan administered twice a day. 
     
     
         14 . The method of  claim 7 , wherein the dosage form contains about 10 mg to about 1000 mg of the bupropion. 
     
     
         15 . The method of  claim 14 , wherein the dosage form contains about 90 mg to about 120 mg of the bupropion. 
     
     
         16 . The method of  claim 7 , wherein the dextromethorphan is in the dosage form. 
     
     
         17 . The method of  claim 16 , wherein the dosage form is solid. 
     
     
         18 . The method of  claim 17 , wherein the dosage form is a tablet, a troche, a pill, or a capsule. 
     
     
         19 . The method of  claim 7 , wherein the dosage form does not contain dextromethorphan. 
     
     
         20 . The method of  claim 19 , wherein the dosage form is solid. 
     
     
         21 . The method of  claim 20 , wherein the dosage form is a tablet, a troche, a pill, or a capsule. 
     
     
         22 . The method of  claim 7 , wherein the dosage form is liquid. 
     
     
         23 . The method of  claim 7 , wherein the dosage form is administered at least once daily or twice daily. 
     
     
         24 . The method of  claim 7 , wherein a sufficient number of units of the dosage form are packaged together to allow administration of a single unit of the dosage form once or twice a day for at least 14 consecutive days. 
     
     
         25 . The method of  claim 7 , wherein a sufficient number of units of the dosage form are packaged together to allow administration of a single unit of the dosage form once or twice a day for at least 30 consecutive days. 
     
     
         26 . A method of preparing a dosage form for increasing dextromethorphan plasma levels comprising:
 mixing a bupropion, a hydroxybupropion, a threohydroxybupropion, or a erythrohydroxybupropion and a pharmaceutically acceptable excipient to form more than one unit of the dosage form; and   wherein a sufficient number of units of the dosage form are packaged together to allow administration of a single unit of the dosage form once or twice a day for at least eight consecutive days;   wherein the dosage form is made available to a human being who is selected for being an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan who will receive the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion with a dextromethorphan for at least eight consecutive days;   wherein the dosage form contains an amount of the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion such that, after eight consecutive days of co-administration of the dosage form, with the dextromethorphan, to a human being that is an extensive metabolizer of dextromethorphan, the C avg  of dextromethorphan in the human being that is at least about 20 times the C avg  of dextromethorphan that would be achieved after administering the same amount of the dextromethorphan without co-administering the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion.   
     
     
         27 . The method of  claim 26 , wherein the dosage form is solid. 
     
     
         28 . The method of  claim 27 , wherein the dosage form is a tablet, a troche, a pill, or a capsule. 
     
     
         29 . The method of  claim 26 , wherein the dosage form is co-administered with about 20 mg to about 200 mg of the dextromethorphan. 
     
     
         30 . The method of  claim 29 , wherein the dextromethorphan is in the dosage form.