Compositions and methods for increasing the metabolic lifetime of dextromethorphan and related pharmacodynamic effects
This disclosure relates to methods administering various compounds in conjunction with dextromethorphan to a human being. Dosage forms, drug delivery systems, and methods related to dextromethorphan or dextrorphan and bupropion, hydroxybupropion, erythrohydroxybupropion, threohydroxybupropion, or a metabolite or prodrug of any of these compounds are also disclosed.
1. A method of increasing metabolic lifetime of dextromethorphan, comprising administering a dosage form comprising bupropion and dextromethorphan 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 the dosage form comprises about 50 mg to about 130 mg of the bupropion; and wherein on the eighth day the dosage form is administered twice a day, the plasma trough level of dextromethorphan is increased at least 15-fold over the plasma trough level of dextromethorphan achieved by administering the same amount of the dextromethorphan without the bupropion twice a day for eight consecutive days.
2. The method of claim 1 , wherein the dosage form comprises about 90 mg to about 120 mg of the bupropion.
3. The method of claim 2 , wherein the dosage form comprises about 100 mg to about 110 mg of the bupropion.
4. The method of claim 2 , wherein the dosage form comprises about 40 mg to about 50 mg of the dextromethorphan.
5. The method of claim 4 , wherein the dosage form comprises about 44 mg to about 46 mg of the dextromethorphan.
6. The method of claim 1 , wherein the dextromethorphan is deuterium-modified.
7. The method of claim 1 , wherein the bupropion is deuterium-modified.
8. The method of claim 1 , wherein on the eighth day the dosage form is administered twice a day the plasma trough level of dextromethorphan is at least about 30 ng/mL.
9. The method of claim 1 , wherein on the eighth day the dosage form is administered twice a day the plasma trough level of dextromethorphan is at least about 40 ng/mL.
10. The method of claim 1 , wherein the dosage form is a solid oral dosage form.
11. A method of increasing metabolic lifetime of dextromethorphan, comprising administering a dosage form comprising about 50 mg to about 160 mg of bupropion and at least about 42 mg of dextromethorphan; wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan; wherein the dosage form is administered twice a day for at least thirty consecutive days; wherein on the eighth day the dosage form is administered twice a day, the plasma trough level of dextromethorphan is increased at least 15-fold over the plasma trough level of dextromethorphan achieved by administering the same amount of the dextromethorphan twice a day without the bupropion for eight consecutive days.
12. The method of claim 11 , wherein the dosage form comprises about 44 mg to about 46 mg of the dextromethorphan.
13. The method of claim 12 , wherein the dosage form comprises about 90 mg to about 120 mg of the bupropion.
14. The method of claim 12 , wherein the dosage form comprises about 100 mg to about 110 mg of the bupropion.
15. The method of claim 11 , wherein the dextromethorphan is deuterium-modified.
16. The method of claim 11 , wherein the bupropion is deuterium-modified.
17. The method of claim 11 , wherein on the eighth day the dosage form is administered twice a day the plasma trough level of dextromethorphan is at least about 30 ng/mL.
18. The method of claim 11 , wherein on the eighth day the dosage form is administered twice a day the plasma trough level of dextromethorphan is at least about 40 ng/mL.
19. The method of claim 11 , wherein the dosage form is a solid oral dosage form.