Method for treating pain with loxapine and amoxapine

• US 20040102434A1
• Filed: 11/20/2003
• Published: 05/27/2004
• Est. Priority Date: 11/26/2002
• Status: Active Grant

• Current Assignee: Alexza Pharmaceuticals Inc. (Grupo Ferrer Internacional SA)
• Original Assignee: Alexza Molecular Delivery Corporation (Grupo Ferrer Internacional SA)
• Inventors: Hale, Ron L., Rabinowitz, Joshua D., Munzar, Patrik
• Granted Patent: US 8,288,372 B2
• Time in Patent Office: Days
• US Class Current: 514/211.13
• CPC Class Codes: A61K 31/553 having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
• CPC Class Codes: A61K 9/007 Pulmonary tract; Aromatherapy
• CPC Class Codes: A61K 9/0073 Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Loxapine, amoxapine, or salts or prodrugs of either, is effective in alleviating pain, particularly headache pain such as migraine, cluster headaches and tension headaches. Preferably the loxapine or amoxapine is administered systemically, most preferably by inhalation.

Claims

1. A method for treating pain in a subject comprising administering to said subject an effective amount of a compound selected from the group consisting of loxapine, pharmaceutically acceptable salts of loxapine and prodrugs of loxapine.

2. A method in accordance with claim 1, wherein said effective amount is an amount sufficient to reduce pain present in said subject.

3. A method in accordance with claim 1, wherein said compound is administered systemically.

4. A method in accordance with claim 1, wherein said pain is selected from the group consisting of migraine pain, cluster headache pain and tension-type headache pain.

5. A method in accordance with claim 4, wherein said pain is migraine pain.

6. A method in accordance with claim 4, wherein said pain is cluster headache pain.

7. A method in accordance with claim 4, wherein said pain is tension-type headache pain.

8. A method in accordance with claim 1 wherein said compound is administered by inhalation.

9. A method in accordance with claim 1, wherein said subject is human, said pain is migraine, and said compound is administered by inhalation.

10. A method in accordance with claim 1, wherein from about 0.3 to about 20 mg of loxapine is administered, or an amount of a salt or prodrug of loxapine is administered that produces in the subject a blood concentration of loxapine equivalent to the administration of from about 0.3 to about 20 mg loxapine.

11. A method in accordance with claim 1, wherein from about 1 to about 10 mg of loxapine is administered, or an amount of a salt or prodrug of loxapine is administered that produces in the subject a blood concentration of loxapine equivalent to the administration of from about 1 to about 10 mg loxapine.

12. A method in accordance with claim 10, wherein administration of the loxapine or salt or prodrug thereof to the subject is conducted so as to result in a maximum blood level of loxapine within about 30 minutes from said administration.

13. A method in accordance with claim 10, wherein administration of the loxapine or salt or prodrug thereof to the subject is conducted so as to result in a maximum blood level of loxapine within about 15 minutes from said administration.

14. A method in accordance with claim 10, wherein administration of the loxapine or salt or prodrug thereof to the subject is conducted so as to result in a peak rate of increase in the blood level of loxapine of at least about 1 ng/ml/minute.

15. A method in accordance with claim 10, wherein administration of the loxapine or salt or prodrug thereof to the subject is conducted so as to result in a blood level of loxapine of at least about 5 ng/ml within about 15 minutes from said administration

16. A method in accordance with claim 1 wherein said compound is administered via inhalation using a rapid-heating drug delivery article or a thin-film drug delivery article.

17. A method in accordance with claim 1, wherein said compound is administered via inhalation delivery device, said compound being vaporized and condensed to provide at least 50% recovery of said compound in an aerosol and wherein said aerosol contains less than about 5% by weight of compound degradation products.

18. A method in accordance with claim 17, wherein said compound is coated on a substrate in the delivery device as thin-film having a film thickness between about 0.5 and 20 μ

m.

19. A method in accordance with claim 1, wherein said compound is administered in the form of an aerosol having a mass median aerodynamic diameter (MMAD) of between about 0.01 and about 3 μ

m.

20. A method in accordance with claim 1, wherein said compound is administered via a rapid heating drug delivery article, said compound being volatized from a compound composition film under conditions sufficient to provide an aerosol having at least 50% recovery of said compound and containing less than about 10% by weight of compound degradation products.

21. A composition for the treatment of pain, said composition comprising (a) an analgesic amount of a compound selected from the group consisting of loxapine, pharmaceutically acceptable salts thereof, and prodrugs thereof, and (b) a pharmaceutically acceptable carrier.

22. A composition of claim 21, further comprising one or more analgesic, antiinflammatory or antimigraine agents.

23. A thin-film composition for the treatment of pain comprising an analgesic amount of a compound selected from the group consisting of loxapine, pharmaceutically acceptable salts thereof and prodrugs thereof, and having a film thickness of from about 0.5 to about 20 μ

m.

24. A method for treating headache pain in a subject comprising administering to said subject an effective amount of a compound selected from the group consisting of loxapine, pharmaceutically acceptable salts of loxapine and prodrugs of loxapine.