Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects
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.
1. A method of increasing dextromethorphan plasma levels in a human being, comprising co-administering between about 50 mg per day and about 250 mg per day of bupropion with dextromethorphan to the human being once or twice a day for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan and in need of treatment with dextromethorphan, wherein the dextromethorphan plasma level on the fifth day bupropion is co-administered with dextromethorphan is at least about 10 times the level that would be achieved by administering the same amount of dextromethorphan without bupropion, and 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 by administering the same amount of dextromethorphan without bupropion for eight consecutive days.
2. The method of claim 1 , wherein the dextromethorphan plasma level on the fifth day bupropion is co-administered with dextromethorphan is at least about 20 times the level that would be achieved by administering the same amount of dextromethorphan without bupropion.
3. The method of claim 1 , wherein bupropion and dextromethorphan are administered in a single dosage form.
4. The method of claim 3 , wherein the single dosage form is a solid.
5. The method of claim 3 , wherein the single dosage form is a liquid.
6. The method of claim 3 , wherein about 30 mg to about 300 mg of dextromethorphan is administered in the single dosage form.
7. The method of claim 3 , wherein about 30 mg to about 120 mg of bupropion is administered in the single dosage form.
8. The method of claim 1 , wherein between about 10 mg per day and about 150 mg per day of dextromethorphan is administered.
9. The method of claim 1 , wherein between about 35 mg per day and about 100 mg per day of dextromethorphan is administered.
10. The method of claim 1 , wherein between about 90 mg per day and about 225 mg per day of bupropion is administered.
11. The method of claim 1 , wherein the AUC 0-12 of dextromethorphan on the eighth day is at least about 400 ng·hr/mL.
12. The method of claim 1 , wherein the AUC 0-12 of dextromethorphan on the eighth day is between about 700 ng·hr/mL and about 1000 ng·hr/mL.
13. The method of claim 1 , wherein a C max of dextromethorphan on the eighth day is between about 70 ng/mL and about 100 ng/mL.
14. A method, comprising co-administering between about 30 mg per day and about 120 mg per day of dextromethorphan with bupropion to a human being in need of treatment with dextromethorphan, wherein dextromethorphan and bupropion are co-administered to the human being once or twice a day for at least eight consecutive days, wherein the co-administration is effective for converting the human being from an extensive metabolizer of dextromethorphan to a lesser metabolizer of dextromethorphan, and 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 by administering the same amount of dextromethorphan without bupropion for eight consecutive days.
15. The method of claim 14 , wherein the co-administration results in an increase of a mean plasma ratio between dextromethorphan and dextrorphan in the human being from 0.01 on the first day of co-administration to 0.71 on the eighth day of co-administration.
16. The method of claim 14 , wherein the co-administration is effective for converting the human being from an extensive metabolizer of dextromethorphan to a poor metabolizer of dextromethorphan.
17. The method of claim 14 , wherein between about 40 mg per day and about 50 mg per day of dextromethorphan is administered.
18. The method of claim 14 , wherein between about 85 mg per day and about 95 mg per day of dextromethorphan is administered.
19. The method of claim 14 , wherein the co-administration of dextromethorphan and bupropion is effective for converting about 100% of the human beings co-administered therewith from an extensive metabolizer of dextromethorphan to a poor metabolizer of dextromethorphan on the eighth day of co-administration.
20. The method of claim 14 , wherein bupropion and dextromethorphan are co-administered together in a single, solid oral dosage form.
21. The method of claim 14 , wherein the AUC 0-12 of dextromethorphan on the eighth day is between about 700 ng·hr/mL and about 1000 ng·hr/mL.
22. The method of claim 21 , wherein the AUC 0-12 of dextromethorphan on the eighth day is between about 800 ng·hr/mL and about 950 ng·hr/mL.
23. The method of claim 14 , wherein a C max of dextromethorphan on the eighth day is between about 50 ng/mL and about 110 ng/mL.
24. The method of claim 23 , wherein the C max of dextromethorphan on the eighth day is between about 70 ng/mL and about 100 ng/mL.