Methods of Administering 3,4-Diaminopyridine

Abstract

Provided herein are methods of determining NAT acetylation status of a subject with a 3,4-DAP-sensitive disease, methods of selecting a dose of 3,4-DAP or a pharmaceutically acceptable salt thereof adjusted to a subject's acetylation status, methods of administering 3,4-diaminopyridine or a pharmaceutically acceptable salt thereof to a patient in need thereof, and methods of treating 3,4-DAP sensitive diseases.

What is claimed is: 
     
         1 . A method of treating a human patient diagnosed with Lambert-Eaton myasthenic syndrome (LEMS) in need of treatment thereof comprising administering a total daily dose of about 30 mg to about 240 mg of 3,4-diaminopyridine (3,4-DAP), or an equivalent amount of a pharmaceutically acceptable salt thereof, to a human patient who is a carrier of two normal function N-acetyl transferase 2 (NAT2) alleles, wherein the total daily dose is optionally provided as a series of divided doses. 
     
     
         2 . The method of  claim 1 , wherein the two normal function NAT2 alleles are wild-type alleles. 
     
     
         3 . The method of  claim 1 , wherein the about 30 mg to about 240 mg of 3,4-DAP is provided via an equivalent amount of 3,4-DAP phosphate salt. 
     
     
         4 . The method of  claim 1 , wherein the total daily dose is about 30 mg to about 100 mg of 3,4-DAP, or an equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         5 . The method of  claim 4 , wherein the total daily dose is about 30 mg to about 80 mg of 3,4-DAP, or an equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         6 . The method of  claim 5 , wherein the total daily dose is about 30 mg to about 50 mg of 3,4-DAP, or an equivalent amount of a pharmaceutically acceptable salt thereof 
     
     
         7 . The method of  claim 4 , wherein the total daily dose is provided via up to 5 divided doses per day. 
     
     
         8 . The method of  claim 7 , wherein the total daily dose is provided via 3 to 4 divided doses per day. 
     
     
         9 . The method of  claim 7 , wherein the total daily dose is provided via 2 to 3 divided doses per day. 
     
     
         10 . The method of  claim 4 , wherein the divided dose is about 10 mg, about 15 mg, about 20 mg, about 25 mg, or about 30 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 4 , wherein the divided dose is provided as one or more scored tablets or portions thereof. 
     
     
         12 . The method of  claim 11 , wherein the scored tablet comprises about 10 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of  claim 4 , wherein the divided dose is provided as an aqueous suspension. 
     
     
         14 . The method of  claim 4 , wherein the total daily dose is about 30 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         15 . The method of  claim 4 , wherein the total daily dose is about 50 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 4 , wherein the total daily dose is about 60 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         17 . The method of  claim 4 , wherein the total daily dose is about 80 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         18 . The method of  claim 4 , wherein the total daily dose is about 100 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         19 . The method of  claim 1 , wherein the patient suffers from renal impairment. 
     
     
         20 . A method of treating a human patient diagnosed with LEMS in need of treatment thereof comprising administering a total daily dose of about 30 mg to about 100 mg of 3,4-DAP, or an equivalent amount of a pharmaceutically acceptable salt thereof, as a series of divided doses to a human patient who is a carrier of two normal function NAT2 alleles. 
     
     
         21 . The method of  claim 20 , wherein the two normal function NAT2 alleles are wild-type alleles. 
     
     
         22 . The method of  claim 20 , wherein the total daily dose is provided via up to 5 divided doses per day. 
     
     
         23 . The method of  claim 22 , wherein the total daily dose is about 30 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         24 . The method of  claim 22 , wherein the total daily dose is about 50 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         25 . The method of  claim 22 , wherein the total daily dose is about 60 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         26 . The method of  claim 22 , wherein the total daily dose is about 80 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         27 . The method of  claim 22 , wherein the total daily dose is about 100 mg of 3,4-DAP, or the equivalent amount of a pharmaceutically acceptable salt thereof. 
     
     
         28 . A method of treating a human patient diagnosed with LEMS in need of treatment thereof comprising administering a total daily dose of 3,4-DAP phosphate salt, which is equivalent to a total daily dose of about 30 mg to about 100 mg of 3,4-DAP, as a series of divided doses to a human patient who is a carrier of two normal function NAT2 alleles. 
     
     
         29 . The method of  claim 28 , wherein the two normal function NAT2 alleles are wild-type alleles.