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 once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions, wherein the once-nightly formulation yields a plasma concentration versus time curve when administered once-nightly in a human subject at a dose of 4.5 g or 6.0 g approximately two hours after a standardized evening meal as depicted in FIG. 12 for the corresponding dose.
2. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions, wherein the once-nightly formulation yields a plasma concentration versus time curve when administered once-nightly in a human subject at a dose of 4.5 g approximately two hours after a standardized evening meal as depicted in FIG. 22 .
3. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions for a human subject in need thereof, wherein the once-nightly formulation yields a dissolution profile as depicted in:
FIG. 7 and FIG. 8 ;
FIG. 20 and FIG. 21 ;
FIG. 3 ; or
FIG. 16 .
4. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 3 , wherein the once-nightly formulation yields a dissolution profile as depicted in FIG. 7 and FIG. 8 .
5. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 3 , wherein the once-nightly formulation yields a dissolution profile as depicted in FIG. 20 and FIG. 21 .
6. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 3 , wherein the once-nightly formulation yields a dissolution profile as depicted in FIG. 3 .
7. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 3 , wherein the once-nightly formulation yields a dissolution profile as depicted in FIG. 16 .
8. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 3 , wherein the once-nightly formulation yields a dissolution profile as depicted in any one of FIGS. 29 through 89 .
9. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions for a human subject in need thereof, wherein the once-nightly formulation yields a dissolution profile between the minimum and maximum values depicted in:
FIG. 25 and FIG. 26 ;
FIG. 27 and FIG. 28 ; or
FIG. 26 and FIG. 28 .
10. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 9 , wherein the once-nightly formulation yields a dissolution profile between the minimum and maximum values depicted in FIG. 25 and FIG. 26 .
11. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 9 , wherein the once-nightly formulation yields a dissolution profile between the minimum and maximum values depicted in FIG. 27 and FIG. 28 .
12. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 1 , wherein the once-nightly formulation yields a dissolution profile between the minimum and maximum values depicted in FIG. 26 and FIG. 28 .
13. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions, wherein the once-nightly formulation yields a plasma concentration versus time curve when administered once-nightly in a human subject at a dose of 4.5 g, 7.5 g or 9.0 g approximately two hours after a standardized evening meal as depicted in FIG. 90 for the corresponding dose.
14. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions, wherein the once-nightly formulation yields a plasma concentration versus time curve when administered once-nightly in a human subject at a dose of 4.5 g, 6.0 g or 7.5 g approximately two hours after a standardized evening meal as depicted in FIG. 13 for the corresponding dose.
15. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions, wherein the once-nightly formulation yields a plasma concentration versus time curve when administered once-nightly in a human subject at a dose of 4.5 g or 6.0 g approximately two hours after a standardized evening meal that is bioequivalent to the plasma concentration versus time curve depicted in FIG. 12 for the corresponding dose.
16. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions, wherein the once-nightly formulation yields a plasma concentration versus time curve when administered once-nightly in a human subject at a dose of 4.5 g approximately two hours after a standardized evening meal that is bioequivalent to the plasma concentration versus time curve depicted in FIG. 22 .
17. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions for a human subject in need thereof, wherein the once-nightly formulation yields a dissolution profile bioequivalent to the profile as depicted in:
FIG. 7 and FIG. 8 ;
FIG. 20 and FIG. 21 ;
FIG. 3 ; or
FIG. 16 .
18. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 17 , wherein the once-nightly formulation yields a dissolution profile bioequivalent to the profile as depicted in FIG. 7 and FIG. 8 .
19. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 17 , wherein the once-nightly formulation yields a dissolution profile bioequivalent to the profile as depicted in FIG. 20 and FIG. 21 .
20. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 17 , wherein the once-nightly formulation yields a dissolution profile bioequivalent to the profile as depicted in FIG. 3 .
21. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 17 , wherein the once-nightly formulation yields a dissolution profile bioequivalent to the profile as depicted in FIG. 16 .
22. The once-nightly modified release formulation of gamma-hydroxybutyrate of claim 17 , wherein the once-nightly formulation yields a dissolution profile bioequivalent to the profile as depicted in any one of FIGS. 29 through 89 .
23. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions, wherein the formulation yields a plasma concentration versus time curve when administered once-nightly in a human subject at a dose of 4.5 g, 7.5 g or 9.0 g approximately two hours after a standardized evening meal that is bioequivalent to the plasma concentration versus time curve depicted in FIG. 90 for the corresponding dose.
24. A once-nightly modified release formulation of gamma-hydroxybutyrate comprising immediate release and modified release portions, wherein the once-nightly formulation yields a plasma concentration versus time curve when administered once-nightly in a human subject at a dose of 4.5 g, 6.0 g or 7.5 g approximately two hours after a standardized evening meal that is bioequivalent to the plasma concentration versus time curve depicted in FIG. 13 for the corresponding dose.