SUSTAINED RELEASE AMINOPYRIDINE COMPOSITION
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 least 12 hours, preferably 24 hours or more and the use of the composition to treat various neurological diseases.
1 . A sustained release tablet comprising:
a sustained release matrix and an aminopyridine, said tablet exhibiting a release profile to obtain a C max :C τ ratio in vivo of about 1.0 to about 3.5 and a predetermined C avSS .
2 . The sustained release tablet of claim 1 wherein said C max :C τ ratio is about 1.5 to about 3.0.
3 . The sustained release tablet of claim 1 wherein said predetermined C axSS is about 21 ng/ml.
4 . The sustained release tablet of claim 1 wherein said predetermined C avSS is about 31 ng/ml.
5 . The sustained release tablet of claim 1 wherein said predetermined C avSS is about 40 ng/ml.
6 . The sustained release tablet of claim 1 wherein said C max :C τ ratio is about 2.0 to about 3.0.
7 . The sustained release tablet of claim 1 wherein said aminopyridine is 4-aminopyridine.
8 . The sustained release table of claim 1 wherein said sustained release matrix is hydroxypropylmethylcellulose.
9 . A method of treating a disease associated with a neurological disorder, said method comprising:
administering an aminopyridine on a dosing regimen to obtain an in vive C max :C τ ratio of 1.0 to 3.5 and a C avSS of about 15 ng/ml to about 35 ng/ml.
10 . The method of claim 9 wherein said C max :C τ ratio is about 1.5 to about 3.0.
11 . The method of claim 9 wherein said C max :C τ ratio is about 2.0 to about 3.0.
12 . The method of claim 9 wherein said neurological disorder comprises a spinal cord injury, Alzheimer's disease, multiple sclerosis, or amyotrophic lateral sclerosis.
13 . The method of claim 9 wherein said neurological disorder comprises a spinal cord injury.
14 . The method of claim 9 wherein said neurological disorder comprises multiple sclerosis.
15 . The method of claim 9 wherein said dosing regimen is comprised of administering a tablet twice daily.
16 . The method of claim 15 wherein said twice daily administration comprises every twelve hours.
17 . The method of claim 9 wherein said aminopyridine comprises 4-aminopyridine.
18 . A therapeutic composition comprised of a release matrix and an active aminopyridine, said aminopyridine being released from said release matrix at a rate to maintain an in vivo C max :C τ ratio of 1.0 to 3.5 and a C avSS of about 15 ng/ml to about 35 ng/ml.
19 . The therapeutic composition of claim 22 wherein said C max :C τ ratio is about 1.5 to about 3.0.
20 . The therapeutic composition of claim 22 wherein said C max :C τ ratio is about 2.0 to about 3.0.
21 . The therapeutic composition of claim 22 wherein the active aminopyridine is 4-aminopyridine.
22 . The therapeutic composition of claim 22 wherein the release matrix is hydroxypropylmethylcellulose.
23 . A sustained release composition comprising:
a sustained release matrix and an aminopyridine, wherein said composition provides a C avSS of about 15 ng/ml to about 35 ng/ml.