Methods of using sustained release aminopyridine compositions
View Patent ↗A pharmaceutical composition which comprises a therapeutically effective amount of a aminopyridine dispersed in a release matrix, including, for example, a composition that can be formulated into a stable, sustained-release oral dosage formulation, such as a tablet which provides, upon administration to a patient, a therapeutically effective plasma level of the aminopyridine for a period of at about 12 hours and the use of the composition to treat various neurological diseases, including multiple sclerosis. A method of selecting individuals based on responsiveness to a treatment, including, for example, identifying individuals who responded to treatment with a sustained release fampridine composition.
1. A method of improving lower extremity function in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release composition of less than 15 milligrams of 4-aminopyridine twice daily for a time period of at least two weeks, wherein the amount of said 4-aminopyridine administered to said patient in each said administering step is the same over said time period.
2. A method of improving lower extremity function in a human multiple sclerosis patient in need thereof comprising orally administering to said patient a sustained release composition of 10 milligrams of 4-aminopyridine twice daily for a time period of at least two weeks.
3. The method of claim 1 , wherein the improving lower extremity function in the patient is increasing walking speed of the patient.
4. The method of claim 1 , wherein the lower extremity function is lower extremity muscle strength.
5. The method of claim 1 , wherein the lower extremity function is lower extremity muscle tone.
6. The method of claim 1 , wherein said method comprises initiating treatment of said patient with 4-aminopyridine by orally administering said sustained release composition twice daily to said patient.
7. The method of claim 2 , wherein said method comprises initiating treatment of said patient with 4-aminopyridine by orally administering said sustained release composition twice daily to said patient.
8. The method of claim 1 , wherein twice daily is about every 12 hours.
9. The method of claim 2 , wherein twice daily is about every 12 hours.
10. The method of claim 1 , wherein said sustained release composition is a tablet.
11. The method of claim 2 , wherein said sustained release composition is a tablet.
12. The method of claim 8 , wherein said sustained release composition is a tablet.
13. The method of claim 9 , wherein said sustained release composition is a tablet.
14. The method of claim 1 , wherein said sustained release composition provides a release profile to obtain a C avSS of about 15 ng/ml to about 35 ng/ml.
15. The method of claim 2 , wherein said sustained release composition provides a release profile to obtain a C avSS of about 15 ng/ml to about 35 ng/ml.
16. The method of claim 1 , wherein said sustained release composition provides a mean T max in a range of about 2 to about 6 hours after administration of the sustained release composition to the patient.
17. The method of claim 2 , wherein said sustained release composition provides a mean T max in a range of about 2 to about 6 hours after administration of the sustained release composition to the patient.
18. The method of claim 1 , wherein said sustained release composition provides a mean T max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.
19. The method of claim 2 , wherein said sustained release composition provides a mean T max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.
20. The method of claim 1 , wherein said sustained release composition is capable of providing, upon administration to the patient, a release profile of the 4-aminopyridine extending over at least 6 hours.
21. The method of claim 2 , wherein said sustained release composition is capable of providing, upon administration to the patient, a release profile of the 4-aminopyridine extending over at least 6 hours.
22. The method of claim 1 , wherein said 4-aminopyridine is dispersed in a rate of release controlling polymer.
23. The method of claim 2 , wherein said 4-aminopyridine is dispersed in a rate of release controlling polymer.
24. The method of claim 1 , wherein said sustained release composition comprises a matrix, in which said 4-aminopyridine is uniformly dispersed, that is suitable for controlling the release rate of the 4-aminopyridine.
25. The method of claim 2 , wherein said sustained release composition comprises a matrix, in which said 4-aminopyridine is uniformly dispersed, that is suitable for controlling the release rate of the 4-aminopyridine.
26. The method of claim 1 , wherein said patient has relapsing remitting multiple sclerosis.
27. The method of claim 2 , wherein said patient has relapsing remitting multiple sclerosis.
28. The method of claim 1 , wherein said time period is more than two weeks.
29. The method of claim 2 , wherein said time period is more than two weeks.
30. The method of claim 1 , wherein said time period comprises twelve weeks.
31. The method of claim 2 , wherein said time period comprises twelve weeks.
32. The method of claim 1 , wherein the lower extremity function is walking.
33. The method of claim 32 , wherein said method comprises initiating treatment of said patient with 4-aminopyridine by orally administering said sustained release composition twice daily to said patient.
34. The method of claim 32 , wherein said sustained release composition is a tablet, and wherein twice daily is about every 12 hours.
35. The method of claim 32 , wherein said sustained release composition provides a release profile to obtain a C avSS of about 15 ng/ml to about 35 ng/ml.
36. The method of claim 2 , wherein the lower extremity function is walking, and wherein said sustained release composition provides a release profile to obtain a C avSS of about 15 ng/ml to about 35 ng/ml.
37. The method of claim 32 , wherein said sustained release composition provides a mean Tmax in a range of about 2 to about 6 hours after administration of the sustained release composition to the patient.
38. The method of claim 2 , wherein the lower extremity function is walking, and wherein said sustained release composition provides a mean T max in a range of about 2 to about 6 hours after administration of the sustained release composition to the patient.
39. The method of claim 32 , wherein said sustained release composition provides a mean T max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.
40. The method of claim 34 , wherein said sustained release composition provides a mean T max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.
41. The method of claim 2 , wherein the lower extremity function is walking, and wherein said sustained release composition provides a mean T max in a range of about 2 to about 5.2 hours after administration of the sustained release composition to the patient.
42. The method of claim 32 , wherein said sustained release composition comprises a matrix, in which said 4-aminopyridine is uniformly dispersed, that is suitable for controlling the release rate of the 4-aminopyridine.
43. The method of claim 2 , wherein the lower extremity function is walking, and wherein said sustained release composition comprises a matrix, in which said 4-aminopyridine is uniformly dispersed, that is suitable for controlling the release rate of the 4-aminopyridine.
44. The method of claim 32 , wherein said time period is more than two weeks.
45. The method of claim 2 , wherein the lower extremity function is walking, and wherein said time period is more than two weeks.
46. The method of claim 32 , wherein said time period comprises twelve weeks.
47. The method of claim 40 , wherein the lower extremity function is walking, and wherein said time period comprises twelve weeks.
48. The method of claim 32 , wherein said sustained release composition is capable of providing, upon administration to the patient, a release profile of the 4-aminopyridine extending over at least 6 hours.
49. The method of claim 2 , wherein the lower extremity function is walking, and wherein said sustained release composition is capable of providing, upon administration to the patient, a release profile of the 4-aminopyridine extending over at least 6 hours.
50. The method of claim 32 , wherein said 4-aminopyridine is dispersed in a rate of release controlling polymer.
51. The method of claim 2 , wherein the lower extremity function is walking, and wherein said 4 -aminopyridine is dispersed in a rate of release controlling polymer.
52. The method of claim 32 , wherein said patient has relapsing remitting multiple sclerosis.