Compositions comprising enzyme-cleavable amphetamine prodrugs and inhibitors thereof
Pharmaceutical compositions and their methods of use are provided, where the pharmaceutical compositions comprise an amphetamine prodrug that provides enzymatically-controlled release of amphetamine or an amphetamine analog. The composition can further comprise an enzyme inhibitor that interacts with the enzyme(s) that mediates the enzymatically-controlled release of amphetamine or the amphetamine analog from the amphetamine prodrug so as to attenuate enzymatic cleavage of the amphetamine prodrug.
1. A method for controlled release of amphetamine to a patient comprising orally administering a pharmaceutical composition to the patient in need thereof, the composition comprising:
a pharmaceutically acceptable carrier; and
a compound of formula AM-1; AM-2; or AM-5:
or a salt, hydrate or solvate thereof.
2. The method of claim 1 , further comprising a GI enzyme inhibitor.
3. The method of claim 2 , wherein the GI enzyme inhibitor is a trypsin inhibitor.
4. The method of claim 1 , wherein the composition comprises a dosage of the compound of from 0.6 mg/kg to 65 mg/kg.
5. The method of claim 1 , wherein the composition comprises a compound of formula AM-1 in a dosage amount of from 4 mg/kg to 32 mg/kg.
6. The method of claim 5 , wherein the composition comprises a compound of formula AM-1 in a dosage amount of about 5 mg/kg.
7. The method of claim 5 , wherein the composition comprises a compound of formula AM-1 in a dosage amount of about 6 mg/kg.
8. The method of claim 5 , wherein the composition comprises a compound of formulate AM-1 in a dosage amount of about 24 mg/kg.
9. The method of claim 5 , wherein the composition comprises a compound of formulate AM-1 in a dosage amount of about 32 mg/kg.
10. The method of claim 1 , wherein the composition comprises a compound of formula AM-2 in a dosage amount of from 4 mg/kg to 64 mg/kg.
11. The method of claim 10 , wherein the composition comprises a compound of formula AM-2 in a dosage amount of about 6 mg/kg.
12. The method of claim 10 , wherein the composition comprises a compound of formulate AM-2 in a dosage amount of about 27 mg/kg.
13. The method of claim 10 , wherein the composition comprises a compound of formulate AM-2 in a dosage amount of about 64 mg/kg.
14. The method of claim 1 , wherein the composition comprises a compound of formula AM-5 in a dosage amount of from 4 mg/kg to 27 mg/kg.
15. The method of claim 14 , wherein the composition comprises a compound of formulate AM-5 in a dosage amount of about 4.5 mg/kg.
16. The method of claim 14 , wherein the composition comprises a compound of formulate AM-5 in a dosage amount of about 22 mg/kg.
17. A method for reducing amphetamine abuse, the method comprising:
orally administering a pharmaceutical composition to a patient, the composition comprising:
a pharmaceutically acceptable carrier; and
a compound of formula AM-1; AM-2; or AM-5:
or a salt, hydrate or solvate thereof.