Sustained Release Aminopyridine Composition

Abstract

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.

What is claimed: 
     
         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 avSS  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 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.   
     
     
         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.