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 compound of formula AM-1; AM-2; or AM-5:
or a salt, hydrate or solvate thereof.
2. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of claim 1 .
3. A composition comprising a GI enzyme inhibitor and a compound of formula AM-1; AM-2; or AM-5:
or a salt, hydrate or solvate thereof.
4. The composition of claim 2 , wherein the composition is formulated for oral administration.
5. The composition of claim 3 , wherein the composition is formulated for oral administration.
6. The composition of claim 3 , wherein the composition comprises a compound of formula AM-1 in a dosage amount of from 4 mg/kg to 32 mg/kg.
7. The composition of claim 3 , wherein the composition comprises a compound of formula AM-1 in a dosage amount of about 5 mg/kg.
8. The composition of claim 3 , wherein the composition comprises a compound of formula AM-1 in a dosage amount of about 6 mg/kg.
9. The composition of claim 3 , wherein the composition comprises a compound of formulate AM-1 in a dosage amount of about 24 mg/kg.
10. The composition of claim 3 , wherein the composition comprises a compound of formulate AM-1 in a dosage amount of about 32 mg/kg.
11. The composition of claim 3 , wherein the composition comprises a compound of formula AM-2 in a dosage amount of from 4 mg/kg to 64 mg/kg.
12. The composition of claim 3 , wherein the composition comprises a compound of formula AM-2 in a dosage amount of about 6 mg/kg.
13. The composition of claim 3 , wherein the composition comprises a compound of formulate AM-2 in a dosage amount of about 27 mg/kg.
14. The composition of claim 3 , wherein the composition comprises a compound of formulate AM-2 in a dosage amount of about 64 mg/kg.
15. The composition of claim 3 , wherein the composition comprises a compound of formula AM-5 in a dosage amount of from 4 mg/kg to 27 mg/kg.
16. The composition of claim 3 , wherein the composition comprises a compound of formulate AM-5 in a dosage amount of about 4.5 mg/kg.
17. The composition of claim 3 , wherein the composition comprises a compound of formulate AM-5 in a dosage amount of about 22 mg/kg.