Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics
Modified release formulations of gamma-hydroxybutyrate having improved dissolution and pharmacokinetic properties are provided, and therapeutic uses thereof.
1. A method of treating a disorder treatable with gamma-hydroxybutyrate in a human in need thereof, the method comprising:
administering a single daily dose to said human, the single daily dose comprising an amount of gamma-hydroxybutyrate equivalent to from 3.0 to 12.0 g of sodium oxybate, wherein the administering comprises
opening a sachet containing a gamma-hydroxybutyrate formulation,
mixing the formulation with water, and
orally administering the mixture.
2. The method of claim 1 , wherein the orally administering occurs at bedtime.
3. The method of claim 1 , wherein the mixing occurs shortly before the orally administering.
4. The method of claim 1 , wherein the orally administering occurs approximately 2 hours after said human has eaten a meal.
5. The method of claim 1 , wherein said administering results in inducing said human to sleep for 6 to 8 hours.
6. The method of claim 1 , wherein the amount of gamma-hydroxybutyrate administered to the human is equivalent to 4.5 g, 6.0 g, 7.5 g, or 9.0 g of sodium oxybate.
7. The method of claim 1 , wherein the mixture is a suspension.
8. The method of claim 1 , wherein the mixing comprises pouring the gamma-hydroxybutyrate formulation from the sachet into a container containing the water.
9. The method of claim 8 , wherein the container contains 50 mL of water prior to the pouring.
10. A method of treating a disorder treatable with gamma-hydroxybutyrate in a human in need thereof, the method comprising:
administering a 4.5 g dose of gamma-hydroxybutyrate to said human that yields a pharmacokinetic profile as shown in FIG. 11 ,
wherein the dose comprises immediate release and modified release portions.
11. A method of treating a disorder treatable with gamma-hydroxybutyrate in a human in need thereof, the method comprising:
administering a modified release formulation of gamma-hydroxybutyrate, comprising immediate release and modified release portions, at a dose of 4.5 g, 6.0 g, or 7.5 g approximately two hours after a standardized evening meal that yields a plasma concentration versus time curve bioequivalent to that depicted in FIG. 12 .
12. A method of treating a disorder treatable with gamma-hydroxybutyrate in a human in need thereof, the method comprising:
administering a modified release formulation of gamma-hydroxybutyrate, comprising immediate release and modified release portions, at a dose of 4.5 g, 6.0 g, or 7.5 g approximately two hours after a standardized evening meal that yields a plasma concentration versus time curve bioequivalent to that depicted in FIG. 13 .
13. A method of treating narcolepsy Type 1 or Type 2, the method comprising:
administering a single daily dose to a human in need thereof, the single daily dose comprising an amount of gamma-hydroxybutyrate equivalent to from 3.0 to 12.0 g of sodium oxybate, wherein the administering comprises
opening a sachet containing a gamma-hydroxybutyrate formulation,
mixing the formulation with water, and
orally administering the mixture.
14. The method of claim 13 , wherein the orally administering occurs at bedtime.
15. The method of claim 13 , wherein the mixing occurs shortly before the orally administering.
16. The method of claim 13 , wherein the orally administering occurs approximately 2 hours after said human has eaten a meal.
17. The method of claim 13 , wherein said administering results in inducing said human to sleep for 6 to 8 hours.
18. The method of claim 13 , wherein the amount of gamma-hydroxybutyrate administered to the human is equivalent to 4.5 g, 6.0 g, 7.5 g, or 9.0 g of sodium oxybate.
19. The method of claim 13 , wherein the mixture is a suspension.
20. The method of claim 13 , wherein the mixing comprises pouring the gamma-hydroxybutyrate formulation from the sachet into a container containing the water.
21. The method of claim 20 , wherein the container contains 50 mL of water prior to the pouring.
22. A method of treatment of narcolepsy Type 1 or Type 2, the method comprising:
administering a single daily dose to a human in need thereof, the single daily dose comprising an amount of gamma-hydroxybutyrate equivalent to from 3.0 to 12.0 g of sodium oxybate,
wherein, compared to a dosing regimen consisting of administering half the dose at t 0 and another half of the dose at t 4h of an immediate release liquid solution of sodium oxybate, the method produces less confusion, less depressive syndrome, less incontinence, less nausea, or less sleepwalking.
23. A method of reducing narcolepsy-related excessive daytime sleepiness or frequency of cataplectic attacks, the method comprising:
administering a single daily dose to a human in need thereof, the single daily dose comprising an amount of gamma-hydroxybutyrate equivalent to from 3.0 to 12.0 g of sodium oxybate, wherein the administering comprises
opening a sachet containing a gamma-hydroxybutyrate formulation,
mixing the formulation with water, and
orally administering the mixture.
24. The method of claim 23 , wherein the orally administering occurs at bedtime.
25. The method of claim 23 , wherein the mixing occurs shortly before the orally administering.
26. The method of claim 23 , wherein the orally administering occurs approximately 2 hours after said human has eaten a meal.
27. The method of claim 23 , wherein said administering results in inducing said human to sleep for 6 to 8 hours.
28. The method of claim 23 , wherein the amount of gamma-hydroxybutyrate administered to the human is equivalent to 4.5 g, 6.0 g, 7.5 g, or 9.0 g of sodium oxybate.
29. The method of claim 23 , wherein the mixture is a suspension.
30. The method of claim 23 , wherein the mixing comprises pouring the gamma-hydroxybutyrate formulation from the sachet into a container containing the water.
31. The method of claim 30 , wherein the container contains 50 mL of water prior to the pouring.