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. An oral pharmaceutical composition for the treatment of narcolepsy, cataplexy, or excessive daytime sleepiness comprising gamma-hydroxybutyrate in a unit dose suitable for administration once daily to a human patient in need thereof, wherein the composition is dose proportional.
2. The oral pharmaceutical composition of claim 1 , wherein the composition is suitable for administration in the evening.
3. The oral pharmaceutical composition of claim 1 , wherein the composition is suitable for administration in the morning.
4. The oral pharmaceutical composition of claim 1 , wherein the composition is dose proportional across 4.5 g, 7.5 g, and 9 g doses of the composition.
5. The oral pharmaceutical composition of claim 1 , wherein the Cmax of the composition is proportional across 4.5 g, 7.5 g, and 9 g doses of the composition.
6. The oral pharmaceutical composition of claim 1 , wherein the composition is dose proportional by a factor of 1 to 1.3.
7. The oral pharmaceutical composition of claim 4 , wherein median T max is between about 1.5 and 2 hours across the increasing doses.
8. The oral pharmaceutical composition of claim 1 , wherein the mean C max is between about 42.9 and 84.5 μg/mL across the increasing doses.
9. The oral pharmaceutical composition of claim 4 , wherein the mean AUC inf is about 191, 358 and 443 μg·h/mL for the 4.5, 7.5 and 9 g doses, respectively.
10. The oral pharmaceutical composition of claim 4 , wherein the mean concentrations at 8 hours are about 4.8, 19.7 and 25.5 μg/mL for the 4.5, 7.5 and 9 g doses, respectively.
11. 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 once daily to a human patient in need thereof, wherein the composition is dose proportional.
12. The method of claim 11 , wherein the composition is administered in the evening.
13. The method of claim 11 , wherein the composition is administered in the morning.
14. The method of claim 11 , wherein the composition is dose proportional across 4.5 g, 7.5 g, and 9 g doses of the composition.
15. The method of claim 11 , wherein the C max of the composition is proportional across 4.5 g, 7.5 g, and 9 g doses of the composition.
16. The method of claim 11 , wherein the composition is dose proportional by a factor of 1 to 1.3.
17. The method of claim 14 , wherein median T max is between about 1.5 and 2 hours across the increasing doses.
18. The method of claim 14 , wherein the mean C max is between about 42.9 and 84.5 μg/mL across the increasing doses.
19. The method of claim 14 , wherein the mean AUC inf is about 191, 358 and 443 μg·h/mL for the 4.5, 7.5 and 9 g doses, respectively.
20. The method of claim 14 , wherein the mean concentrations at 8 hours are about 4.8, 19.7 and 25.5 μg/mL for the 4.5, 7.5 and 9 g doses, respectively.