Compositions and methods of using threohydroxybupropion for therapeutic purposes

• US 9,402,843 B2
• Filed: 01/21/2015
• Issued: 08/02/2016
• Est. Priority Date: 11/05/2013
• Status: Active Grant

• Current Assignee: Antecip Bioventures II LLC
• Original Assignee: Antecip Bioventures II LLC
• Inventors: Tabuteau, Herriot
• Primary Examiner(s): BARSKY, JARED
• Application Number:
  US14/602,177
• Publication Number:
  US 20150133485A1
• Time in Patent Office: 559 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 31/138 Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377
• CPC Class Codes: A61K 31/4748 forming part of bridged ring systems strychnine A61K31/475; morphinan derivatives A61K31/485
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031

Abstract

This disclosure relates to methods administering threohydroxybupropion or a prodrug thereof in conjunction with dextromethorphan to a human being. Dosage forms, drug delivery systems, and methods related to dextromethorphan or dextrorphan and threohydroxybupropion or a prodrug of threohydroxybupropion are also disclosed.

Claims

1. A method of increasing dextromethorphan plasma levels in a human being, comprising co-administering threohydroxybupropion with dextromethorphan to the human being for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein threohydroxybupropion and dextromethorphan are the sole active agents administered to the human being, wherein the threohydroxybupropion is administered in an amount that results in an AUC_0-12 of dextromethorphan that is at least 40 ng·

hr/mL, and wherein, on the eighth day that threohydroxybupropion and dextromethorphan are co-administered, the AUC_0-12 of dextromethorphan is at least 20 times the AUC_0-12 of dextromethorphan that would result from administering the same amount of dextromethorphan without threohydroxybupropion.

2. The method of claim 1, wherein the AUC_0-12 of dextromethorphan is at least 50 ng·

hr/mL.

3. The method of claim 1, wherein the AUC_0-12 of dextromethorphan on the eighth day is at least 100 ng·

hr/mL.

4. The method of claim 1, wherein the AUC_0-12 of dextromethorphan on the eighth day is at least 400 ng·

hr/mL.

5. The method of claim 1, wherein the AUC_0-12 of dextromethorphan on the eighth day is at least 700 ng·

hr/mL.

6. The method of claim 1, wherein the AUC_0-24 of dextromethorphan on the eighth day is at least 100 ng·

hr/mL.

7. The method of claim 1, wherein the AUC_0-24 of dextromethorphan on the eighth day is at least 1000 ng·

hr/mL.

8. The method of claim 1, wherein the AUC_0-inf of dextromethorphan on the eighth day is at least 100 ng·

hr/mL.

9. The method of claim 1, wherein the AUC_0-inf of dextromethorphan on the eighth day is at least 2000 ng·

hr/mL.

10. The method of claim 1, wherein the AUC_0-inf of dextromethorphan on the eighth day is at least 3000 ng·

hr/mL.

11. A method of increasing dextromethorphan plasma levels in a human being, comprising co-administering threohydroxybupropion with dextromethorphan to the human being for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein threohydroxybupropion and dextromethorphan are the sole active agents administered to the human being, wherein the threohydroxybupropion is administered in an amount that results in a C_max of dextromethorphan that is at least 6 ng/mL, and wherein, on the eighth day that threohydroxybupropion and dextromethorphan are co-administered, the AUC_0-12 of dextromethorphan is at least 20 times the AUC_0-12 of dextromethorphan that would result from administering the same amount of dextromethorphan without threohydroxybupropion.

12. The method of claim 11, wherein the C_max of dextromethorphan on the eighth day is at least 10 ng/mL.

13. The method of claim 11, wherein the C_max of dextromethorphan on the eighth day is at least 60 ng/mL.

14. The method of claim 11, wherein the C_max of dextromethorphan on the eighth day is at least 80 ng/mL.

15. A method of increasing dextromethorphan plasma levels in a human being, comprising co-administering threohydroxybupropion with dextromethorphan to the human being for at least eight consecutive days, wherein the human being is an extensive metabolizer of dextromethorphan in need of treatment with dextromethorphan, wherein threohydroxybupropion and dextromethorphan are the sole active agents administered to the human being, wherein the threohydroxybupropion is administered in an amount that results in a C_avg of dextromethorphan, over the period between two separate and consecutive administrations of dextromethorphan, that is at least 5 ng/mL, and wherein, on the eighth day that threohydroxybupropion and dextromethorphan are co-administered, the AUC_0-12 of dextromethorphan is at least 20 times the AUC_0-12 of dextromethorphan that would result from administering the same amount of dextromethorphan without threohydroxybupropion.

16. The method of claim 15, wherein the threohydroxybupropion is administered in an amount that results in a C_avg of dextromethorphan, over the period between two separate and consecutive administrations of dextromethorphan, that is at least 60 ng/mL.

17. The method of claim 15, wherein the C_avg of dextromethorphan on the eighth day is at least 8 ng/mL, wherein the C_avg is for the period between two separate and consecutive administrations of dextromethorphan, or if dextromethorphan is administered only once on the eighth day, the C_avg is for 12 hours after the only dose of dextromethorphan on the eighth day.

18. The method of claim 15, wherein the C_avg of dextromethorphan on the eighth day is at least 30 ng/mL, wherein the C_avg is for the period between two separate and consecutive administrations of dextromethorphan, or if dextromethorphan is administered only once on the eighth day, the C_avg is for 12 hours after the only dose of dextromethorphan on the eighth day.