Method of therapeutic administration of DHE to enable rapid relief of migraine while minimizing side effect profile

• US 8,119,639 B2
• Filed: 07/19/2010
• Issued: 02/21/2012
• Est. Priority Date: 02/11/2007
• Status: Active Grant

• Current Assignee: MAP Pharmaceuticals, Inc. (Abbvie Incorporated)
• Original Assignee: MAP Pharmaceuticals, Inc. (Abbvie Incorporated)
• Inventors: Cook, Robert O., Shrewsbury, Stephen B., Ramadan, Nabih N., Armer, Thomas A.
• Primary Examiner(s): Anderson, James D
• Application Number:
  US12/839,190
• Publication Number:
  US 20100284940A1
• Time in Patent Office: 582 Days
• Field of Search: 514/250
• US Class Current: 514/250
• CPC Class Codes: A61K 31/10 Sulfides; Sulfoxides; Sulfones
• CPC Class Codes: A61K 31/48 Ergoline derivatives, e.g. lysergic acid, ergotamine
• CPC Class Codes: A61K 31/4985 Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
• 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: A61K 9/0075 for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

Pharmaceutical compositions containing dihydroergotamine (DHE) and methods in which DHE is administered to patients for treatment of migraine without side effects or adverse effects are disclosed. Methods for rapid treatment of migraine with DHE are disclosed comprising: dampening the peak plasma concentration (C_max) and slightly delaying the peak such as to avoid activating the dopaminergic and adrenergic receptors, while achieving sufficient active binding to the serotonin receptors to provide relief from migraine symptoms within a timeframe that permits rapid resolution of migraine symptoms. Inhaler devices suitable for the methods are disclosed. Kits for practicing the methods of invention are disclosed.

Claims

1. A method of providing rapid treatment of migraine, said method comprising administering a total dose of dihydroergotamine mesylate to a human suffering from migraine via pulmonary administration, wherein the dihydroergotamine mesylate is administered at a rate that provides:

a mean peak plasma concentration (C_max) of dihydroergotamine of less than 40,000 pg/ml within a mean time to C_max (T_max) that is less than 20 minutes after administration; and

a C_max of 8′

-OH dihydroergotamine of less than 1,000 pg/ml, wherein the total dose of dihydroergotamine mesylate that is administered ranges from 0.1 to 10 mg per migraine.

2. The method of claim 1, wherein the mean peak plasma concentration (C_max) of 8′

-OH dihydroergotamine is less than 500 pg/ml.

3. The method of claim 2, wherein the mean peak plasma concentration (C_max) of dihydroergotamine is less than 20,000 pg/ml.

4. The method of claim 3, wherein the mean peak plasma concentration (C_max) of dihydroergotamine is less than 15,000 pg/ml.

5. The method of claim 1, wherein the mean T_max of dihydroergotamine is within 15 minutes following administration.

6. The method of claim 1, wherein the total dose ranges from 0.5 mg to 5.0 mg per migraine.

7. The method of claim 1, wherein the dihydroergotamine mesylate is administered by oral inhalation using a dry powder inhaler, nebulizer, vaporizer, pressurized metered dose inhaler, or a breath activated pressurized metered dose inhaler.

8. The method of claim 7, wherein the dihydroergotamine mesylate is administered by a breath activated pressurized metered dose inhaler.

9. The method of claim 7, wherein the dihydroergotamine mesylate is administered by a dry powder inhaler.

10. The method of claim 8, wherein the breath activated pressurized metered dose inhaler comprises a plume control feature.

11. The method of claim 8, wherein the breath activated pressurized metered dose inhaler comprises a vortexing chamber.

12. The method of claim 1, wherein the total dose ranges from 1.0 mg to 2.0 mg per migraine.

13. The method of claim 1, wherein the human suffering from migraine is suffering from a migraine with aura.

14. A method of providing rapid treatment of migraine, said method comprising administering a unit dose of dihydroergotamine mesylate to a human suffering from migraine via pulmonary administration, wherein the dihydroergotamine mesylate is administered at a rate that provides:

a mean time to C_max (T_max) of dihydroergotamine that is less than 20 minutes after administration, and a mean area under a curve of a concentration of dihydroergotamine in systemic circulation versus time (AUC) is within 75% of a comparable intravenous (IV) delivered dose; and

a C_max of 8′

-OH dihydroergotamine of less than 1,000 pg/ml, wherein the unit dose of dihydroergotamine mesylate is less than 2.0 mg.