Methods of treating parkinson's disease

Abstract

The present disclosure relates to (a) carbidopa prodrugs, (b) pharmaceutical combinations and compositions comprising a carbidopa prodrug and/or an L-dopa prodrug, and (c) methods of treating Parkinson's disease and associated conditions comprising administering a carbidopa prodrug and an L-dopa prodrug to a subject with Parkinson's disease.

1 - 30 . (canceled) 
     
     
         31 . A method of delivering dopamine to a human Parkinson's disease patient comprising: administering to the patient via continuous subcutaneous administration for about 16 hours to about 24 hours:
 (a) a first compound, which is carbidopa 3′-monophosphate, carbidopa 3′,4′-diphosphate, a carbidopa salt, or carbidopa, at a dose of at least about 1.25 mg/kg of the first compound; and   (b) a second compound, which is levodopa 3′-monophosphate, levodopa 3′,4′-diphosphate, a levodopa salt, or levodopa, at a dose of at least about 5 mg/kg of the second compound;   wherein the first compound and the second compound are formulated in the same aqueous pharmaceutical formulation,   wherein the method is sufficient to achieve, within 8 hours since the start of the continuous subcutaneous administration and without co-administration of a catechol-O-methyl transferase inhibitor, a steady state levodopa plasma level of at least about 1000 ng/ml in the patient that lasts for at least 8 hours.   
     
     
         32 . The method of  claim 31 , wherein the first compound is administered at a dose of from about 1.25 mg/kg to about 5 mg/kg, and the second compound is administered at a dose of from about 5 mg/kg to about 45.9 mg/kg. 
     
     
         33 . The method of  claim 32 , wherein the first compound is carbidopa 3′-monophosphate. 
     
     
         34 . The method of  claim 32 , wherein the first compound is carbidopa 3′,4′-diphosphate. 
     
     
         35 . The method of  claim 32 , wherein the first compound is carbidopa. 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 32 , wherein the first compound is a carbidopa salt. 
     
     
         39 . The method of  claim 32 , wherein the second compound is levodopa 3′-monophosphate. 
     
     
         40 . The method of  claim 32 , wherein the second compound is levodopa 3′,4′-diphosphate. 
     
     
         41 . The method of  claim 32 , wherein the second compound is levodopa. 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . The method of  claim 32 , wherein the second compound is a levodopa salt. 
     
     
         45 . The method of  claim 32 , wherein the first compound is a carbidopa salt, and the second compound is a levodopa salt. 
     
     
         46 . The method of  claim 32 , wherein the pharmaceutical formulation further comprises one or more pharmaceutically acceptable excipients. 
     
     
         47 . The method of  claim 32 , wherein the pharmaceutical formulation further comprises a pH adjusting agent. 
     
     
         48 . The method of  claim 32 , wherein the pH of the pharmaceutical formulation is equal to or greater than about 8.8. 
     
     
         49 . The method of  claim 32 , wherein the pharmaceutical formulation further comprises a buffering agent. 
     
     
         50 . The method of  claim 31 , wherein the method is sufficient to achieve the steady state levodopa plasma level in the patient for at least 16 hours. 
     
     
         51 . The method of  claim 31 , wherein the method is sufficient to achieve the steady state levodopa plasma level in the patient for at least 24 hours. 
     
     
         52 . The method of  claim 31 , wherein the steady state levodopa plasma level in the patient is achieved without an oral medication for Parkinson's Disease. 
     
     
         53 . The method of  claim 31 , wherein the steady state levodopa plasma level is from about 1000 ng/ml to about 3000 ng/ml. 
     
     
         54 . The method of  claim 31 , wherein the steady state levodopa plasma level is from about 1000 ng/ml to about 2000 ng/ml. 
     
     
         55 . A method of delivering dopamine to a human Parkinson's disease patient comprising: administering to the patient via continuous subcutaneous administration for about 16 hours to about 24 hours:
 (a) a first compound, which is carbidopa 3′-monophosphate, carbidopa 3′,4′-diphosphate, a carbidopa salt, or carbidopa, at a dose of at least about 1.25 mg/kg of the first compound; and   (b) a second compound, which is levodopa 3′-monophosphate, levodopa 3′,4′-diphosphate, a levodopa salt, or levodopa, at a dose of at least about 5 mg/kg of the second compound;   wherein the first compound and the second compound are formulated in separate aqueous pharmaceutical formulations,   wherein the method is sufficient to achieve, within 8 hours since the start of the continuous subcutaneous administration and without co-administration of a catechol-O-methyl transferase inhibitor, a steady state levodopa plasma level of at least about 1000 ng/ml in the patient that lasts for at least 8 hours.   
     
     
         56 . A method of delivering dopamine to a human Parkinson's disease patient comprising: administering to the patient via continuous subcutaneous administration for about 16 hours to about 24 hours:
 (a) a first compound, which is a carbidopa salt or carbidopa, at a dose of at least about 1.25 mg/kg of the first compound; and   (b) a second compound, which is a levodopa salt or levodopa, at a dose of at least about 5 mg/kg of the second compound;   wherein the first compound and the second compound are formulated in the same aqueous pharmaceutical formulation,   wherein the method is sufficient to achieve, within 8 hours since the start of the continuous subcutaneous administration and without co-administration of a catechol-O-methyl transferase inhibitor, a steady state levodopa plasma level of at least about 1000 ng/ml in the patient that lasts for at least 8 hours.   
     
     
         57 . An aqueous pharmaceutical composition, which is suitable for continuous subcutaneous administration, comprising:
 (a) a first compound, which is carbidopa 3′-monophosphate, carbidopa 3′,4′-diphosphate, a carbidopa salt, or carbidopa; and   (b) a second compound, which is levodopa 3′-monophosphate, levodopa 3′,4′-diphosphate, a levodopa salt, or levodopa;   wherein continuous subcutaneous administration of the composition to a Parkinson's disease patient for about 16 hours to about 24 hours at a dose of at least about 1.25 mg/kg of the first compound and at least about 5 mg/kg of the second compound is sufficient to achieve, within 8 hours since the start of the continuous subcutaneous administration and without co-administration of a catechol-O-methyl transferase inhibitor, a steady state levodopa plasma level of at least about 1000 ng/ml in the patient that lasts for at least 8 hours.   
     
     
         58 . A kit comprising the composition of  claim 57 , and instructions for use.