Compositions and methods comprising erythrohydroxybupropion and related compounds for improving the efficacy of dextromethorphan

1. A method of increasing the metabolic lifetime of dextromethorphan, comprising co-administering erythrohydroxybupropion or bupropion with dextromethorphan to a human being once or twice a day for at least eight consecutive days, wherein erythrohydroxybupropion or bupropion is administered in an amount that results in an AUC 0-12 of erythrohydroxybupropion in the human being, on day 8, that is at least about 200 ng·hr/mL, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein the co-administration results in an AUC 0-12 of dextromethorphan that on the eighth day, is at least about 20 times the AUC 0-12 that would be achieved b administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion for eight consecutive days, and wherein dextromethorphan is present in the body of the human being at the same time as erythrohydroxybupropion or bupropion.

2. The method of claim 1 , wherein an increase in the dextromethorphan plasma level occurs on the first day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, as compared to the same amount of dextromethorphan administered without erythrohydroxybupropion or bupropion.

3. The method of claim 2 , wherein the dextromethorphan plasma level on the first day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, is at least twice the level that would be achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion.

4. The method of claim 1 , wherein, on the fifth day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, the dextromethorphan plasma level is higher than the dextromethorphan plasma level that would have been achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion for five consecutive days.

5. The method of claim 4 , wherein the dextromethorphan plasma level, on the fifth day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, is at least 20 times the level that would be achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion for five consecutive days.

6. The method of claim 1 , wherein, on the sixth day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, the dextromethorphan plasma level is higher than the dextromethorphan plasma level that would have been achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion for six consecutive days.

7. The method of claim 6 , wherein the dextromethorphan plasma level, on the sixth day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, is at least 30 times the level that would be achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion for six consecutive days.

8. The method of claim 1 , wherein dextromethorphan has a plasma level 12 hours after co-administering erythrohydroxybupropion or bupropion with dextromethorphan that is at least twice the plasma level that would be achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion.

9. The method of claim 8 , wherein, after the first co-administration of erythrohydroxybupropion or bupropion with dextromethorphan, dextromethorphan has a plasma level 12 hours after co-administering erythrohydroxybupropion or bupropion with dextromethorphan that is at least twice the plasma level that would be achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion.

10. The method of claim 1 , wherein, on the fifth day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, dextromethorphan has a plasma level 12 hours after co-administering erythrohydroxybupropion or bupropion with dextromethorphan that is at least 40 times the plasma level that would be achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion.

11. The method of claim 1 , wherein, on the sixth day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, dextromethorphan has a plasma level 12 hours after co-administering erythrohydroxybupropion or bupropion with dextromethorphan that is at least 50 times the plasma level that would be achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion.

12. The method of claim 1 , wherein, on the seventh day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, dextromethorphan has a plasma level 12 hours after co-administering erythrohydroxybupropion or bupropion with dextromethorphan that is at least 70 times the plasma level that would be achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion.

13. The method of claim 1 , wherein, on the eighth day that erythrohydroxybupropion or bupropion and dextromethorphan are co-administered, dextromethorphan has a plasma level 12 hours after co-administering erythrohydroxybupropion or bupropion with dextromethorphan that is at least 80 times the plasma level that would be achieved by administering the same amount of dextromethorphan without erythrohydroxybupropion or bupropion.

14. The method of claim 1 , wherein the human patient is at risk pf experiencing an adverse event as a result of being treated with dextromethorphan and the adverse event is reduced by the co-administration.