Methods for providing rapid relief of motor fluctuations in a parkinson's disease patient

Abstract

The present invention provides methods of providing rapid relief of motor fluctuations in a Parkinson's disease patient. The methods of the invention comprise pulmonary administration of levodopa by inhalation at therapeutically effective concentrations such that the patient's plasma levodopa concentration increases by at least about 200 ng/ml within 10 minutes or less post inhalation as compared to the concentration of levodopa in the patient's plasma prior to inhalation of the levodopa and wherein the patient's plasma concentration remains increased by at least about 200 ng/ml for a time period of at least 15 minutes after inhalation. The methods of the invention are particularly useful for treatment of motor fluctuations which arise as a result of poorly controlled levodopa plasma levels in a patient.

1 . A method of providing rapid relief of motor fluctuations in a Parkinson's disease patient comprising:
 administering at least one dose of levodopa by inhalation to a Parkinson's disease patient;   wherein within about 10 minutes of administration of levodopa by inhalation, the patient's plasma levodopa concentration increases by at least about 200 ng/ml as compared to the patient's plasma levodopa concentration prior to administration; and   wherein said patient's plasma levodopa concentration maintains said increase of at least about 200 ng/ml for a time period of at least about 15 minutes after administration.   
     
     
         2 . The method of  claim 1 , wherein the dose comprises about 10 mg to about 75 mg of levodopa. 
     
     
         3 . The method of  claim 1 , wherein the dose contains a salt. 
     
     
         4 . The method of  claim 1 , wherein the dose contains a phospholipid. 
     
     
         5 . The method of  claim 1 , wherein the AUC of levodopa in the patient's plasma at about 10 minutes after administration of a dose of levodopa by inhalation, is increased by at least about 1000 ng-min/ml for every 4 mg of levodopa administered as compared to the patient's plasma levodopa concentration prior to administration of levodopa by inhalation. 
     
     
         6 . The method of  claim 1 , wherein the AUC of said levodopa in the plasma at about 10 minutes after administration of a dose of levodopa by inhalation is increased by at least about 1000-1500 ng-min/ml for every 4 mg of levodopa administered as compared to the patient's plasma levodopa concentration prior to administration of levodopa by inhalation. 
     
     
         7 . The method of  claim 1 , wherein the dose comprises about 12 mg to about 35 mg of levodopa. 
     
     
         8 . The method of  claim 1 , further comprising co-administering a dopa decarboxylase inhibitor to the patient. 
     
     
         9 . The method of  claim 1 , wherein the patient's plasma levodopa concentration maintains said increase of at least about 200 ng/ml for a time period of at least about 20 minutes after administration. 
     
     
         10 . The method of  claim 1 , wherein the patient's plasma levodopa concentration maintains said increase of at least about 200 ng/ml for a time period of at least about 30 minutes after administration. 
     
     
         11 . The method of  claim 1 , wherein the patient's plasma levodopa concentration maintains said increase of at least about 200 ng/ml for a time period of at least about 60 minutes after administration. 
     
     
         12 . The method of  claim 1 , wherein the dose of levodopa comprises at least about 10 mg of levodopa. 
     
     
         13 . The method of  claim 1 , wherein said patient's plasma levodopa concentration does not increase more than about 1000 ng/ml within 10 minutes. 
     
     
         14 - 30 . (canceled) 
     
     
         31 . The method of  claim 1 , wherein said dosages of levodopa are not affected by a central nervous system food effect. 
     
     
         32 - 34 . (canceled) 
     
     
         35 . The method of  claim 8 , wherein the dopa decarboxylase inhibitor is administered to the patient before, simultaneously with or after, administration of levodopa by inhalation. 
     
     
         36 . The method of  claim 1 , wherein the dose of levodopa comprises 90% by dry weight levodopa, 8% by dry weight dipalmitoylphosphatidylcholine (DPPC) and 2% sodium chloride. 
     
     
         37 . (canceled) 
     
     
         38 . A method of providing rapid relief of motor fluctuations in a Parkinson's disease patient comprising:
 administering levodopa to said patient such that the patient's plasma levodopa levels increase by about 200-500 ng/ml.   
     
     
         39 . The method of  claim 38 , wherein said levodopa is administered by the oral route, pulmonary route or parenteral route. 
     
     
         40 . The method of  claim 38 , wherein said plasma levodopa levels are increased by 200-400 ng/ml, 300-400 ng/ml, 350-450 ng/ml or about 400 ng/ml. 
     
     
         41 . The method of  claim 38 , wherein said levodopa is administered by the pulmonary route and is at a dose of about 25-40 mg of levodopa to the pulmonary system. 
     
     
         42 . The method of  claim 38 , wherein said patient has at least a 100% improvement in UPDRS score within 20 minutes of administering said levodopa. 
     
     
         43 - 63 . (canceled)