Non-sedating antihistamine injection formulations and methods of use thereof

• US 8,513,259 B2
• Filed: 09/21/2011
• Issued: 08/20/2013
• Est. Priority Date: 07/03/2009
• Status: Active Grant

• Current Assignee: JDP Therapeutics, LLC
• Original Assignee: JDP Therapeutics, Inc.
• Inventors: Du, Jie
• Primary Examiner(s): RICCI, CRAIG D
• Application Number:
  US13/238,453
• Publication Number:
  US 20120010217A1
• Time in Patent Office: 699 Days
• Field of Search: None
• US Class Current: 514/255.04
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14

Abstract

Described herein are injectable compositions containing non-sedating or second and third generation antihistamines such as cetirizine/levocetirizine and methods of use thereof. Specifically, methods of treating acute urticaria or angioedema associated with an acute allergic reaction are disclosed. In certain embodiments, the injectable compositions are bioequivalent to currently marketed oral dosage forms with the same number of mg of cetirizine.

Claims

1. A method of increasing peak plasma concentration and/or providing immediate onset of plasma concentration of cetirizine in an individual in need of treatment for acute urticaria or angioedema associated with an acute allergic reaction, comprising

administering to the individual an intravenous injection of an injectable cetirizine composition containing 2 mg to 20 mg of cetirizine at a rate of 10 mg per 1.0-1.5 minutes or faster,

wherein the peak plasma concentration (Cmax) of the intravenous injectable cetirizine composition is greater than twice the Cmax of a reference immediate-release oral cetirizine dosage form having the same number of mg of cetirizine as the injectable cetirizine composition, and wherein the area under the plasma time curve measured as AUC_0-36 hr and AUC_0-inf is substantially the same for the intravenously injectable cetirizine composition and the reference immediate-release oral cetirizine dosage form.

2. The method of claim 1, wherein the peak plasma concentration (Cmax) of the intravenous injectable cetirizine composition is about 4.2 times that of the Cmax of the reference immediate-release oral cetirizine dosage form.

3. The method of claim 1, wherein administering the intravenous injection does not substantially increase the side effect of drowsiness compared to the reference immediate-release oral cetirizine dosage form.

4. The method of claim 1, wherein administering the intravenous injection does not substantially increase the side effect of dry mouth compared to the reference oral cetirizine dosage form.

5. The method of claim 1, wherein the mean Cmax for a 10 mg reference immediate-release oral cetirizine dosage form is about 318 ng/ml and the mean Cmax for a 10 mg injectable formulation via intravenous administration is about 1345 ng/ml hr.

6. The method of claim 1, wherein the mean AUC_0-36 for a 10 mg reference immediate-release oral cetirizine dosage form and a 10 mg injectable formulation via intravenous administration is about 2550-2640 ng/ml hr., and the mean AUC_0-INF is about 2650-2772 ng/ml hr.

7. The method of claim 1, wherein the area under the plasma time curve for the injectable formulation via intravenous administration measured as AUC_0-1hr is at about twice as large as the AUC_0-1hr for a reference immediate-release oral cetirizine dosage form having the same number of mg of cetirizine as the injectable cetirizine composition.

8. The method of claim 1, wherein the area under the plasma time curve for the injectable formulation via intravenous administration measured as AUC_0-2hr is at about 1.5 times as large as the AUC_0-2hr for a reference immediate-release oral cetirizine dosage form having the same number of mg of cetirizine as the injectable cetirizine composition.

9. The method of claim 1, wherein the acute allergic reaction includes anaphylaxis.

10. The method of claim 1, wherein the injectable cetirizine composition contains 5 mg to 20 mg of cetirizine.