Claims for Patent: 9,198,905

Summary for Patent: 9,198,905

Title:	Compositions and methods for reducing dextrorphan plasma levels and related pharmacodynamic effects
Abstract:	This disclosure relates to methods of decreasing dextrorphan plasma levels comprising co-administering hydroxybupropion, or a prodrug thereof, and dextromethorphan to a human being in need of treatment with dextromethorphan. Dosage forms, drug delivery systems, and methods related to dextromethorphan and hydroxybupropion or a prodrug of bupropion are also disclosed.
Inventor(s):	Herriot Tabuteau
Assignee:	Antecip Bioventures II LLC
Application Number:	US14/550,618
Patent Claims:	1. A method of increasing the metabolic lifetime of dextromethorphan, comprising co-administering hydroxybupropion or bupropion with dextromethorphan to a human being once or twice a day for at least eight consecutive days, wherein hydroxybupropion or bupropion is administered in an amount that results in an AUC0-12 of hydroxybupropion in the human being, on the eighth day, that is at least about 3,000 ng·hr/mL, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, and wherein the co-administration results in an AUC0-12 of dextromethorphan that, on the eighth day, is at least about 20 times the AUC0-12 that would be achieved by administering the same amount of dextromethorphan without hydroxybupropion or a bupropion for eight consecutive days and wherein dextromethorphan is present in the body of the human being at the same time as hydroxybupropion or bupropion. 2. The method of claim 1, wherein an increase in the dextromethorphan plasma level occurs on the first day that hydroxybupropion or bupropion and dextromethorphan are co-administered, as compared to the same amount of dextromethorphan without hydroxybupropion or bupropion. 3. The method of claim 2, wherein the dextromethorphan plasma level on the first day that hydroxybupropion 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 hydroxybupropion or bupropion. 4. The method of claim 1, wherein, on the fifth day that hydroxybupropion 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 hydroxybupropion or bupropion. 5. The method of claim 4, wherein the dextromethorphan plasma level, on the fifth day that hydroxybupropion 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 hydroxybupropion or bupropion for five consecutive days. 6. The method of claim 1, wherein, on the sixth day that hydroxybupropion 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 hydroxybupropion or bupropion for six consecutive days. 7. The method of claim 6, wherein the dextromethorphan plasma level, on the sixth day that hydroxybupropion 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 hydroxybupropion or bupropion for six consecutive days. 8. The method of claim 1, wherein dextromethorphan has a plasma level 12 hours after co-administering hydroxybupropion or bupropion with dextromethorphan that is at least twice the plasma level that would be achieved by administering the same amount of dextromethorphan without hydroxybupropion or bupropion. 9. The method of claim 8, wherein, after the first co-administration of hydroxybupropion or bupropion with dextromethorphan, dextromethorphan has a plasma level 12 hours after co-administering hydroxybupropion or bupropion with dextromethorphan that is at least twice the plasma level that would be achieved by administering the same amount of dextromethorphan without hydroxybupropion or bupropion. 10. The method of claim 1, wherein, on the fifth day that hydroxybupropion or bupropion and dextromethorphan are co-administered, dextromethorphan has a plasma level 12 hours after co-administering hydroxybupropion 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 hydroxybupropion or bupropion. 11. The method of claim 1, wherein, on the sixth day that hydroxybupropion or bupropion and dextromethorphan are co-administered, dextromethorphan has a plasma level 12 hours after co-administering hydroxybupropion 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 hydroxybupropion or bupropion. 12. The method of claim 1, wherein, on the seventh day that hydroxybupropion or bupropion and dextromethorphan are co-administered, dextromethorphan has a plasma level 12 hours after co-administering hydroxybupropion 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 hydroxybupropion or bupropion. 13. The method of claim 1, wherein, on the eighth day that hydroxybupropion or bupropion and dextromethorphan are co-administered, dextromethorphan has a plasma level 12 hours after co-administering hydroxybupropion 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 hydroxybupropion 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. 15. A method of decreasing the number of doses of dextromethorphan from three to six times a day to once or twice a day without loss of efficacy, comprising orally co-administering hydroxybupropion or bupropion with dextromethorphan to a human being once or twice a day for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein hydroxybupropion or bupropion is administered in an amount that results in an AUC0-12 of hydroxybupropion in the human being, on the eighth day, that is at least about 3,000 ng·hr/mL, wherein the co-administration results in an AUC0-12 of dextromethorphan that on the eighth day, is at least about 20 times the AUC0-12 that would be achieved b administering the same amount of dextromethorphan without hydroxybupropion or bupropion for eight consecutive days. 16. The method of claim 15, wherein dextromethorphan is administered twice a day, and the treatment is at least as effective as administering the same amount of dextromethorphan four times a day without administering hydroxybupropion or bupropion. 17. The method of claim 15, wherein dextromethorphan is administered twice a day, and the treatment is at least as effective as administering the same amount of dextromethorphan three times a day without administering hydroxybupropion or bupropion. 18. The method of claim 15, wherein about 35 mg to about 120 mg of dextromethorphan is administered per day.