Granted Patent B2

US 9,422,223 · App. 14/881,379 · Granted Aug 23, 2016

Inventors: Ken Phares (Chapel Hill, NC); David Mottola (Cary, NC); Roger Jeffs (Chapel Hill, NC)

Assignee: United Therapeutics Corporation

C07C59/13A61K9/0053A61K31/192A61K31/216A61K31/223A61K31/235C07C51/412C07C59/70C07C69/712C07C229/08C07C235/06C07C235/08C07C259/06C07F9/091C07F9/117C07C2103/10

Abstract

Claims (16)

1. An oral pharmaceutical formulation: comprising a treprostinil diethanolamine, which has an absolute bioavailability of at least 15% upon oral administration to a human subject, wherein said formulation when orally administered to the human subject a) provides a linear increase over 8 hours of a Cmax in a plasma of the human subject with a dose of at least 0.05 mg administered orally to the human subject and b) maintains a concentration of treprostinil in the plasma of the human subject of at least 50 pg/ml for at least 8 hours.

2. The oral pharmaceutical formulation of claim 1 , wherein the absolute bioavailability of said treprostinil diethanolamine ranges from 21 to 25% upon oral administration to the human subject.

3. The oral pharmaceutical formulation of claim 1 , wherein the oral bioavailability of the treprostinil diethanolamine is at least 50% greater than the oral bioavailability of treprostinil as free acid.

4. The oral pharmaceutical formulation of claim 1 , wherein the oral bioavailability of the treprostinil diethanolamine is at least 100% greater than the oral bioavailability of treprostinil as free acid.

5. An oral pharmaceutical formulation: comprising a treprostinil diethanolamine, which has an absolute bioavailability of at least 15% upon oral administration to a human subject, wherein said formulation when orally administered to the human subject a) provides a linear increase over 8 hours of a AUCinf in a plasma of the human subject with a dose of at least 0.05 mg administered orally to the human subject and b) maintains a concentration of treprostinil in the plasma of the human subject of at least 50 pg/ml for at least 8 hours.

6. The oral pharmaceutical formulation of claim 5 , wherein the absolute bioavailability of said treprostinil diethanolamine ranges from 21 to 25% upon oral administration to the human subject.

7. The oral pharmaceutical formulation of claim 5 , wherein the oral bioavailability of the treprostinil diethanolamine is at least 50% greater than the oral bioavailability of treprostinil as free acid.

8. The oral pharmaceutical formulation of claim 5 , wherein the oral bioavailability of the treprostinil diethanolamine is at least 100% greater than the oral bioavailability of treprostinil as free acid.

9. The oral pharmaceutical formulation of claim 1 , wherein the formulation comprises 0.125 mg of the treprostinil diethanolamine.

10. The oral pharmaceutical formulation of claim 1 , wherein the formulation comprises 0.25 mg of the treprostinil diethanolamine.

11. The oral pharmaceutical formulation of claim 1 , wherein the formulation comprises 1 mg of the treprostinil diethanolamine.

12. The oral pharmaceutical formulation of claim 5 , wherein the formulation comprises 0.125 mg of the treprostinil diethanolamine.

13. The oral pharmaceutical formulation of claim 5 , wherein the formulation comprises 0.25 mg of the treprostinil diethanolamine.

14. The oral pharmaceutical formulation of claim 5 , wherein the formulation comprises 1 mg of the treprostinil diethanolamine.

15. The oral pharmaceutical formulation of claim 1 , wherein the dose is no more than 2 mg of the treprostinil diethanolamine.

16. The oral pharmaceutical formulation of claim 5 , wherein the dose is no more than 2 mg of the treprostinil diethanolamine.

Continuity (9)