Compositions and methods for opioid antagonist delivery
Disclosed in certain embodiments is a pharmaceutical formulation (e.g., parenteral formulation) comprising a therapeutically effective amount of nalmefene or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable adjuvant (e.g., parenterally acceptable adjuvant) that promotes the rate at which the nalmefene or salt thereof is more rapidly absorbed into the systemic circulation of a subject identified as in need thereof.
1. A parenteral formulation comprising a therapeutically effective amount of nalmefene or a pharmaceutically acceptable salt thereof and a parenterally acceptable adjuvant comprising magnesium chloride at a concentration ranging from about 0.5% (w/v) to about 1% (w/v), wherein the formulation provides a time to onset of opioid antagonistic action of less than 5 minutes post administration via an intramuscular or subcutaneous injection to a subject experiencing an opioid agonist overdose.
2. The parenteral formulation of claim 1 , wherein the formulation provides a mean time to maximum plasma concentration of nalmefene of about 2.0 hours or less post an intramuscular administration to a population of healthy subjects.
3. The parenteral formulation of claim 2 , wherein the formulation provides a mean time to maximum plasma concentration of nalmefene of about 1.0 hour or less post an intramuscular administration to a population of healthy subjects.
4. The parenteral formulation of claim 1 , wherein the formulation provides a time to clinically manifested onset of opioid antagonistic action of about 4 minutes or less post intramuscular or subcutaneous injection to a subject experiencing an opioid agonist overdose.
5. The parenteral formulation of claim 2 , wherein the formulation provides a mean time to maximum plasma concentration of nalmefene of about 1.5 hours or less post intramuscular injection to a population of healthy subjects.
6. The parenteral formulation of claim 3 , wherein the formulation provides a mean time to maximum plasma concentration of nalmefene of about 0.5 hour or less post an intramuscular administration to a population of healthy subjects.
7. The parenteral formulation of claim 1 , wherein the formulation provides a time to clinically manifested onset of opioid antagonistic action of less than 5 minutes post intramuscular injection to a subject experiencing an opioid agonist overdose.
8. The parenteral formulation of claim 1 , wherein the formulation provides a time to clinically manifested onset of opioid antagonistic action of less than 5 minutes post subcutaneous injection to a subject experiencing an opioid agonist overdose.
9. The parenteral formulation of claim 2 , wherein the adjuvant promotes the systemic absorption rate and/or the total amount absorbed of the nalmefene or pharmaceutically acceptable salt thereof post injection as compared to the same formulation but without the adjuvant.
10. The parenteral formulation of claim 2 , comprising nalmefene hydrochloride.
11. A method of providing opioid overdose rescue to a subject comprising intramuscularly or subcutaneously administering to a subject in need thereof a parenteral formulation comprising a therapeutically effective amount of nalmefene or a pharmaceutically acceptable salt thereof and magnesium chloride at a concentration ranging from about 0.5% (w/v) to about 1% (w/v), wherein the formulation provides a time to onset of opioid antagonistic action of less than 5 minutes post administration via an intramuscular or subcutaneous injection to a subject experiencing an opioid agonist overdose.
12. A method of preparing a subject prior to entering a locale having a potentially toxic level of an opioid such that the subject is protected from experiencing an opioid overdose as a result of entering the locale, said preparation comprising administering to the subject prior to the subject entering the locale a parenteral formulation comprising a therapeutically effective amount of nalmefene or a pharmaceutically acceptable salt thereof and magnesium chloride at a concentration ranging from about 0.5% (w/v) to about 1% (w/v), wherein the formulation provides a mean time to maximum plasma concentration of nalmefene of about 2.0 hours or less post an intramuscular administration to a population of healthy subjects.
13. A drug delivery system comprising an injection device containing a parenteral formulation of claim 2 .
14. The drug delivery system of claim 13 , wherein the parenteral formulation is disposed within a pre-filled syringe, a vial, an injection pen, or an auto-injector.
15. The parenteral formulation of claim 1 , wherein the magnesium chloride is at a concentration of about 0.9%.
16. The method of claim 11 , wherein the magnesium chloride is at a concentration of about 0.9%.
17. The method of claim 12 , wherein the magnesium chloride is at a concentration of about 0.9%.