Gamma-hydroxybutyrate compositions having improved pharmacokinetics in the fed state
Oral pharmaceutical compositions of sodium oxybate having improved pharmacokinetic properties when administered less than two hours after eating are provided, and therapeutic uses thereof.
1. An oral pharmaceutical composition for the treatment of narcolepsy, cataplexy, or excessive daytime sleepiness comprising gamma-hydroxybutyrate in a unit dose suitable for administration less than two hours after eating.
2. The oral pharmaceutical composition of claim 1 , wherein the composition is suitable for administrating with food, immediately after eating, up to 30 minutes after eating, up to 1 hours after eating, or up to 1.5 hours after eating.
3. The oral pharmaceutical composition of claim 1 , wherein the composition is administered once daily.
4. The oral pharmaceutical composition of claim 1 , wherein the composition is suitable for administration in the evening.
5. The oral pharmaceutical composition of claim 1 , wherein the composition is suitable for administration in the morning.
6. The oral pharmaceutical composition of claim 1 , wherein the composition comprises gamma-hydroxybutyrate in an extended release or delayed release formulation.
7. The oral pharmaceutical composition of claim 1 , wherein the composition comprises gamma-hydroxybutyrate in a modified release formulation.
8. The oral pharmaceutical composition of claim 1 , wherein the composition provides a substantially similar fed state PK profile and 2 hours post meal administration PK profile.
9. The oral pharmaceutical composition of claim 1 , wherein the composition provides a mean AUC inf when administered less than two hours after eating that is 50%-120% of the mean AUC inf when the composition is administered at least two hours after eating.
10. The oral pharmaceutical composition of claim 1 , wherein the composition provides a mean AUC inf when administered less than two hours after eating that is 50%-120% of the mean AUC inf when the composition is administered while fasting.
11. The oral pharmaceutical composition of claim 10 , wherein the composition provides a mean AUC inf when administered less than two hours after eating that is 80%-95% of the mean AUC inf when the composition is administered while fasting.
12. The oral pharmaceutical composition of claim 11 , wherein the composition provides a mean AUC inf when administered less than two hours after eating that is 85%-90% of the mean AUC inf when the composition is administered while fasting.
13. The oral pharmaceutical composition of claim 1 , wherein the composition provides a mean C max when administered less than two hours after eating that is 50%-120% of the mean C max when the composition is administered at least two hours after eating.
14. The oral pharmaceutical composition of claim 1 , wherein the composition provides a mean C max when administered less than two hours after eating that is 50%-120% of the mean C max when the composition is administered while fasting.
15. The oral pharmaceutical composition of claim 14 , wherein the composition provides a mean C max when administered less than two hours after eating that is 55%-80% of the mean C max when the composition is administered while fasting.
16. The oral pharmaceutical composition of claim 15 , wherein the composition provides a mean C max when administered less than two hours after eating that is 60%-75% of the mean C max when the composition is administered while fasting.
17. The oral pharmaceutical composition of claim 1 , wherein the composition provides a C max that is dose proportional.
18. The oral pharmaceutical composition of claim 1 , wherein the composition provides no dose dumping.
19. The oral pharmaceutical composition of claim 1 , wherein there is no significant reduction in safety or efficacy to a patient following administration.
20. The oral pharmaceutical composition of claim 1 , wherein the composition provides an AUC inf bioequivalent to an AUC inf of an equal dose of immediate release liquid solution of sodium oxybate administered at to and to in equally divided doses at least two hours after eating.
21. The oral pharmaceutical composition of claim 1 , wherein the composition provides a C max that is less than the C max of an equal dose of immediate release liquid solution of sodium oxybate administered at to and to in equally divided doses at least two hours after eating.
22. The oral pharmaceutical composition of claim 1 , wherein the composition provides a C max that is less than the C max of an equal dose of immediate release liquid solution of sodium oxybate administered at to and to in equally divided doses less than two hours after eating.
23. The oral pharmaceutical composition of claim 1 , wherein the composition provides a C max that is 10-60% less than the C max of an equal dose of immediate release liquid solution of sodium oxybate administered at to and to in equally divided doses at least two hours after eating.
24. The oral pharmaceutical composition of claim 1 , wherein the composition provides a C max that is 10-60% less than the C max of an equal dose of immediate release liquid solution of sodium oxybate administered at to and to in equally divided doses less than two hours after eating.
25. The oral pharmaceutical composition of claim 1 , wherein the composition provides a change in C max between when the composition is administered at least two hours after eating and when the composition is administered less than two hours after eating that is 10-60% less than the change in C max of an equal dose of immediate release liquid solution of sodium oxybate administered at to and to in equally divided doses at least two hours after eating.
26. The oral pharmaceutical composition of claim 1 , wherein the composition provides a change in C max between when the composition is administered at least two hours after eating and when the composition is administered less than two hours after eating that is 10-60% less than the change in C max of an equal dose of immediate release liquid solution of sodium oxybate administered at to and to in equally divided doses less than two hours after eating.
27. The oral pharmaceutical composition of claim 1 , wherein the composition provides an AUC that is more dose proportional than the AUC of an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses at least two hours after eating.
28. The oral pharmaceutical composition of claim 1 , wherein the composition provides an AUC that is more dose proportional than the AUC of an equal dose of immediate release liquid solution of sodium oxybate administered at t 0 and t 4h in equally divided doses less than two hours after eating.
29. An oral pharmaceutical composition comprising gamma-hydroxybutyrate in a unit dose suitable for administration less than two hours after eating.