GAMMA-HYDROXYBUTYRATE COMPOSITIONS HAVING IMPROVED PHARMACOKINETICS IN THE FED STATE

1 . A method of treating narcolepsy and associated disorders and symptoms in a patient in need thereof comprising:

administering an oral pharmaceutical composition comprising gamma-hydroxybutyrate less than two hours after eating.

2 . The method of claim 1 , wherein the oral pharmaceutical composition is administered once daily.

3 . The method of 1, wherein administration is immediately after eating, up to 30 minutes after eating, up to 1 hour after eating, up to 1.5 hours after eating, or up to 2 hours after eating.

4 . The method of claim 1 , wherein the composition is effective to induce sleep for at least six consecutive hours, at least eight consecutive hours, or at least ten consecutive hours.

5 . The oral pharmaceutical composition of claim 1 , wherein the composition comprises gamma-hydroxybutyrate in an extended release or delayed release formulation.

6 . The method of claim 1 , wherein the composition comprises gamma-hydroxybutyrate in a modified release formulation.

7 . The method of claim 1 , wherein the composition provides a substantially similar fed state PK profile and 2 hour post meal administration PK profile.

8 . The method of claim 1 , wherein the composition provides a mean AUC inf when administered less than two hour after eating that is 50%-120% of the mean AUC inf when the composition is administered at least two hours after eating or when the composition is administered while fasting.

9 . The method of claim 1 , wherein the composition when administered less than two hour after eating provides a mean AUC inf with a 90% CI that falls within the 80-125% bioequivalence range of an equal dose of the composition administered in the fasted state with no effect boundaries.

10 . The method of claim 1 , wherein the composition provides a mean C max when administered less than two hour after eating that is 50%-120% of the mean C max when the composition is administered at least two hours after eating or when the composition is administered while fasting.

11 . The method of claim 1 , wherein the composition provides a C max that is dose proportional.

12 . The method of claim 1 , wherein the composition provides no dose dumping.

13 . The method of claim 1 , wherein there is no significant reduction in safety or efficacy to a patient following administration.

14 . The method 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 t 0 and t 4h in equally divided doses at least two hours after eating.

15 . The method 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 t 0 and t 4h in equally divided doses at least two hours after eating.

16 . The method 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 t 0 and t 4h in equally divided doses less than two hours after eating.

17 . The method 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 t 0 and t 4h in equally divided doses at least two hours after eating.

18 . The method 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 t 0 and t 4h in equally divided doses less than two hours after eating.

19 . The method 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.

20 . The method 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.

21 . The method of claim 1 , wherein the absorption of the gamma-hydroxybutyrate in the gastro-intestinal tract is not substantially changed by the presence of food.

22 . The method of claim 1 , wherein the administration is effective to treat narcolepsy Type 1 or Type 2.

23 . The method of claim 1 , wherein the composition is suitable for administration in the evening or in the morning.

24 . The method of claim 1 , wherein the composition is a dry particulate formulation is in a sachet, stick-pack, or discrete packaging unit.

25 . The method of claim 24 , further comprising gamma-hydroxybutyrate in amounts equivalents to 0.5 g, 1.0 g, 1.5 g, 3.0 g, 4.5 g, 6.0 g, 7.5 g, 9.0 g, 10.5 g or 12 g of sodium oxybate in each sachet, stick-pack, or discrete packaging unit.

26 . The method of claim 25 , further comprising opening the sachet or stick-pack, mixing the composition with water shortly before administration.

27 . The method of claim 26 , further comprising mixing the composition with 50 mL water prior to administration.

28 . The method of claim 27 , wherein the administering is to a patient sitting in bed.

29 . A method of treating narcolepsy and associated disorders and symptoms in a patient in need thereof comprising:

administering an oral pharmaceutical composition comprising gamma-hydroxybutyrate to a patient in a fed state.

30 . A method of treating narcolepsy and associated disorders and symptoms in a patient in need thereof comprising:

administering an oral pharmaceutical composition comprising gamma-hydroxybutyrate to a patient in a fasted state with no effect boundaries or in a fed state.