COMPOSITIONS AND METHODS FOR EMERGENCY RESCUE
Disclosed in certain embodiments is a parenteral formulation comprising a therapeutically effective amount of an emergency rescue active pharmaceutical ingredient and a parenterally acceptable adjuvant in an amount that enhances the absorption of the emergency rescue active pharmaceutical ingredient (ER-API) into the systemic circulation. The enhanced absorption may be evidence by a faster onset time, a faster T max and/or a greater C max and/or a greater AUC last and/or a greater AUC 0.25 and/or a greater AUC 0.5 and/or a greater AUC 0.75 and/or a greater AUC 1 and/or increased bioavailability as compared to formulations without the adjuvant.
1 . A parenteral formulation comprising a therapeutically effective amount of an emergency rescue active pharmaceutical ingredient (ER-API) and a parenterally acceptable absorption enhancing amount of adjuvant, wherein ER-API is not an opioid antagonist.
2 . The parenteral formulation of claim 1 , wherein the formulation promotes the systemic absorption rate of the ER-API upon injection as compared to the same formulation without the adjuvant.
3 . The parenteral formulation of claim 1 , wherein the formulation provides a shorter time to onset of emergency rescue action upon intramuscular or subcutaneous injection to a subject experiencing an allergic reaction or poisoning as compared to the same formulation without the adjuvant.
4 . The parenteral formulation of claim 1 , wherein the ER-API is epinephrine or a pharmaceutically acceptable salt thereof.
5 . The parenteral formulation of claim 1 , wherein the ER-API is atropine or a pharmaceutically acceptable salt thereof.
6 . The parenteral formulation of claim 1 , wherein the formulation provides a time to onset of emergency rescue action of about 5 minutes or less, about 4 minutes or less, about 3 minutes or less, about 2 minutes or less, and about 1 minute or less, post intramuscular or subcutaneous injection to a subject experiencing an allergic reaction or poisoning.
7 . The parenteral formulation of claim 1 , wherein the formulation provides a mean time to maximum plasma concentration of the ER-API of about 2.0 hours or less post intramuscular or subcutaneous administration to a population of healthy subjects.
8 . The parenteral formulation of claim 1 , wherein the formulation provides a mean time to maximum plasma concentration of the ER-API of about 1.5 hours or less, about 1 hour or less, about 0.75 hour or less, about 0.5 hour or less, about 20 minutes or less, about 15 minutes or less, about 10 minutes or less, about 5 minutes or less, about 3 minutes or less or about 1 minute or less post intramuscular or subcutaneous injection to a population of healthy subjects.
9 . The parenteral formulation of claim 1 , wherein the adjuvant comprises magnesium chloride.
10 . The parenteral formulation of claim 1 , wherein the adjuvant increases the rate of systemic absorption of the ER-API upon intramuscular or subcutaneous injection.
11 . The parenteral formulation of claim 1 , wherein the adjuvant is present in the parenteral formulation from about 0.1% (w/v) to about 50% (w/v).
12 . A method of providing emergency rescue to a subject experiencing an allergic reaction or poisoning, comprising intramuscularly or subcutaneously administering to a subject in need thereof a formulation of claim 1 .
13 . A drug delivery system comprising an injection device containing a formulation of claim 1 .
14 . A kit comprising a therapeutically effective amount of an emergency rescue active pharmaceutical ingredient (ER-API) and an absorption enhancing amount of a parenterally acceptable adjuvant, wherein the ER-API and the adjuvant are independently in a solution form or in a powder form, and wherein the ER-API and the adjuvant are stored either in separate containers or in one container.
15 . The kit of claim 14 , wherein the ER-API is epinephrine or pharmaceutically acceptable salt thereof.
16 . The kit of claim 14 , wherein the ER-API is atropine or a pharmaceutically acceptable salt thereof.
17 . The kit of claim 14 , wherein the adjuvant is magnesium chloride.
18 . The kit of claim 14 , wherein the injection device is an auto-injector.
19 . The kit of claim 18 , wherein the auto-injector is pre-filled with a solution of the ER-API, a solution of the parenterally acceptable adjuvant, or both.
20 . The kit of claim 14 , further comprising a syringe and a needle.