Nucleotide hemi-sulfate salt for the treatment of hepatitis C virus
A hemi-sulfate salt of the structure: to treat a host infected with hepatitis C, as well as pharmaceutical compositions and dosage forms, including solid dosage forms, thereof.
1. A compound of the formula:
2. A solid dosage form comprising a compound of the formula
that provides a steady-state trough plasma level (C 24,ss ) of metabolite
between approximately 20-60 ng/mL.
3. The solid dosage form of claim 2 , wherein the steady-state trough plasma level (C 24,ss ) is between approximately 20-50 ng/mL.
4. The solid dosage form of claim 2 , wherein the steady-state trough plasma level (C 24,ss ) is between approximately 20-45 ng/mL.
5. The solid dosage form of claim 2 , wherein the steady-state trough plasma level (C 24,ss ) is between approximately 20-30 ng/mL.
6. The solid dosage form of claim 2 , wherein the steady-state trough plasma level (C 24,ss ) is between approximately 20-25 ng/mL.
7. The solid dosage form of claim 2 , wherein the area under the curve of metabolite
is between approximately 1,500 ng*h/mL and 3,000 ng*h/mL.
8. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 1,800 ng*h/mL and 3,000 ng*h/mL.
9. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 2,100 ng*h/mL and 3,000 ng*h/mL.
10. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 2,400 ng*h/mL and 3,000 ng*h/mL.
11. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 2,700 ng*h/mL and 3,000 ng*h/mL.
12. The solid dosage form of claim 7 , wherein the area under the curve is between approximately 2,000 ng*h/mL and 2,200 ng*h/mL.
13. A pharmaceutical composition comprising an anti-HCV effective amount of a compound of the formula
in a pharmaceutically acceptable carrier.
14. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers at least 300 mg of the compound.
15. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers at least 400 mg of the compound.
16. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers at least 500 mg of the compound.
17. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers at least 600 mg of the compound.
18. The pharmaceutical composition of claim 17 , wherein the solid dosage form provides a steady-state trough plasma level (C 24,ss ) of metabolite
between approximately 20-60 ng/mL.
19. The pharmaceutical composition of claim 18 , wherein the steady-state trough plasma level (C 24,ss ) is between approximately 40-60 ng/mL.
20. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers at least 700 mg of the compound.
21. The pharmaceutical composition of claim 13 , in a solid dosage form that delivers approximately 600 mg of the compound.
22. The pharmaceutical composition of claim 13 , wherein the solid dosage form provides a steady-state trough plasma level (C 24,ss ) of metabolite
between approximately 20-60 ng/mL.
23. The pharmaceutical composition of claim 22 , wherein the solid steady-state trough plasma level (C 24,ss ) is between approximately 20-50 ng/mL.
24. The pharmaceutical composition of claim 22 , wherein the solid steady-state trough plasma level (C 24,ss ) is between approximately 20-45 ng/mL.
25. The pharmaceutical composition of claim 22 , wherein the solid steady-state trough plasma level (C 24,ss ) is between approximately 20-30 ng/mL.
26. The pharmaceutical composition of claim 22 , wherein the solid steady-state trough plasma level (C 24,ss ) is between approximately 20-25 ng/mL.
27. The pharmaceutical composition of claim 13 , wherein the pharmaceutically acceptable carrier is suitable for oral delivery.
28. The pharmaceutical composition of claim 27 , wherein the pharmaceutically acceptable carrier is in the form of a tablet.
29. A method to treat a hepatitis C infection, in a human in need thereof, comprising administering an effective amount of a compound of the formula
optionally in a pharmaceutically acceptable carrier to the human in need thereof.
30. The method of claim 29 , wherein the compound is administered orally.
31. The method of claim 29 , wherein the compound is administered parenterally.
32. The method of claim 29 , wherein at least 300 mg of the compound is administered.
33. The method of claim 29 , wherein at least 400 mg of the compound is administered.
34. The method of claim 29 , wherein at least 500 mg of the compound is administered.
35. The method of claim 29 , wherein at least 600 mg of the compound is administered.
36. The method of claim 29 , wherein at least 700 mg of the compound is administered.
37. The method of claim 29 , wherein at least 800 mg of the compound is administered.
38. The method of claim 29 , wherein the compound is administered for up to 12 weeks.
39. The method of claim 38 , wherein the compound is administered once a day.
40. The method of claim 38 , wherein the compound is administered every other day.
41. The method of claim 29 , wherein the compound is administered for up to 8 weeks.
42. The method of claim 29 , wherein the compound is administered for up to 6 weeks.
43. The method of claim 29 , wherein the compound is administered for at least 6 weeks.
44. The method of claim 29 , wherein the compound is administered for at least 8 weeks.
45. The method of claim 29 , wherein the compound is administered for at least 12 weeks.
46. The method of claim 29 , wherein the hepatitis C virus is Genotype 1a, 1b, 2a, 2b, 3a, 4a, 4d, 5a, or 6.
47. The method of claim 46 , wherein the hepatitis C virus is Genotype 1a or 1b.
48. The method of claim 46 , wherein the hepatitis C virus is Genotype 2a or 2b.
49. The method of claim 46 , wherein the hepatitis C virus is Genotype 3a.
50. The method of claim 46 , wherein the hepatitis C virus is Genotype 4a or 4b.
51. The method of claim 46 , wherein the hepatitis C virus is Genotype 5a.
52. A solid dosage form comprising a compound of the formula