Compositions and methods comprising bupropion or related compounds for sustained delivery of dextromethorphan

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 obtaining clinically significant blood levels of dextromethorphan comprising co-administering to a human being for at least eight consecutive days a combination of:
 a. a bupropion, a hydroxybupropion, a threohydroxybupropion, or a erythrohydroxybupropion; with   b. a dextromethorphan;   wherein co-administration of the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, with the dextromethorphan results in a fluctuation index value of the dextromethorphan plasma level on the eighth day that is less than 80% and a dextromethorphan C avg  that is at least 30 ng.hr/mL.   
     
     
         2 . The method of  claim 1 , wherein at least about 35 mg of the dextromethorphan is administered twice a day. 
     
     
         3 . The method of  claim 1 , wherein about 50 mg to about 130 mg of the bupropion is administered twice a day. 
     
     
         4 . The method of  claim 1 , wherein about 44 mg to about 45 mg of the dextromethorphan is administered twice a day. 
     
     
         5 . The method of  claim 1 , wherein about 100 mg to about 105 mg of the bupropion is administered twice a day. 
     
     
         6 . The method of  claim 4 , wherein about 100 mg to about 105 mg of the bupropion is administered twice a day. 
     
     
         7 . The method of  claim 1 , wherein the bupropion has an at least 90% enantiomeric excess of R- or S-enantiomer or the dextromethorphan contains deuterium. 
     
     
         8 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 5% to about 60%. 
     
     
         9 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 30% to about 60%. 
     
     
         10 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 40% to about 60%. 
     
     
         11 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 60% to about 80%. 
     
     
         12 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 10% to about 40%. 
     
     
         13 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 20% to about 40%. 
     
     
         14 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 20% to about 30%. 
     
     
         15 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 25% to about 30%. 
     
     
         16 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 30% to about 40%. 
     
     
         17 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 30% to about 35%. 
     
     
         18 . The method of  claim 1 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 35% to about 40%. 
     
     
         19 . A method of decreasing fluctuation of dextromethorphan plasma levels comprising co-administering to a human being, twice a day for at least eight consecutive days, a combination of:
 a. a bupropion, a hydroxybupropion, a threohydroxybupropion, or a erythrohydroxybupropion; with   b. a dextromethorphan;   wherein co-administration of the bupropion, the hydroxybupropion, the threohydroxybupropion, or the erythrohydroxybupropion, with the dextromethorphan results in a fluctuation index value of the dextromethorphan plasma level on the eighth day that is less than 50%.   
     
     
         20 . The method of  claim 19 , wherein at least about 42 mg of the dextromethorphan is administered twice a day. 
     
     
         21 . The method of  claim 19 , wherein about 50 mg to about 160 mg of the bupropion is administered twice a day. 
     
     
         22 . The method of  claim 19 , wherein about 45 mg to about 46 mg of the dextromethorphan is administered twice a day. 
     
     
         23 . The method of  claim 19 , wherein about 105 mg to about 110 mg of the bupropion is administered twice a day. 
     
     
         24 . The method of  claim 20 , wherein about 100 mg to about 105 mg of the bupropion is administered twice a day. 
     
     
         25 . The method of  claim 19 , wherein the bupropion has an at least 90% enantiomeric excess of R- or S-enantiomer or the dextromethorphan contains deuterium. 
     
     
         26 . The method of  claim 19 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 5% to about 40%. 
     
     
         27 . The method of  claim 19 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 10% to about 30%. 
     
     
         28 . The method of  claim 19 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 10% to about 20%. 
     
     
         29 . The method of  claim 19 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 5% to about 15%. 
     
     
         30 . The method of  claim 19 , wherein the fluctuation index value of the dextromethorphan plasma level on the eighth day is about 10% to about 15%.