Methods of therapeutic monitoring of nitrogen scavenging drugs

Abstract

The present disclosure provides methods for evaluating daily ammonia exposure based on a single fasting ammonia blood level measurement, as well as methods that utilize this technique to adjust the dosage of a nitrogen scavenging drug, determine whether to administer a nitrogen scavenging drug, and treat nitrogen retention disorders.

1 .- 11 . (canceled) 
     
     
         12 . A method of treating a subject with a urea cycle disorder who has previously been administered an initial dosage of glyceryl tri-[4-phenylbutyrate], and who has a fasting plasma ammonia level less than the upper limit of normal for plasma ammonia level, the method comprising:
 (a) measuring a fasting plasma ammonia level for the subject by analyzing, a plasma sample from the subject that has been stored at 0-15° C.;   (b) comparing the fasting plasma ammonia level to the upper limit of normal for plasma ammonia level; and   (c) if the fasting plasma ammonia level is greater than half the upper limit of normal for plasma ammonia level, administering an increased dosage of glyceryl tri-[4-phenylbutyrate].   
     
     
         13 . The method of  claim 12 , wherein the plasma sample is analyzed within 3 hours of collection. 
     
     
         14 . The method of  claim 12 , wherein the plasma sample is analyzed within less than 1 hour of collection. 
     
     
         15 . The method of  claim 12 , wherein the plasma sample is analyzed immediately after collection. 
     
     
         16 . The method of  claim 12 , further comprising repeating steps (a) to (c) until the subject exhibits a fasting plasma ammonia level at or below half the upper limit of normal for plasma ammonia level. 
     
     
         17 . The method of  claim 12 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L. 
     
     
         18 . The method of  claim 12 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally. 
     
     
         19 . A method of treating a subject with a urea cycle disorder who has previously been administered an initial dosage of glyceryl tri-[4-phenylbutyrate], and who has a fasting plasma ammonia level less than the upper limit of normal for plasma ammonia level, the method comprising:
 (a) measuring a fasting plasma ammonia level for the subject by analyzing a plasma sample from the subject that has been stored at below 0° C.;   (b) comparing the fasting plasma ammonia level to the upper limit of normal for plasma ammonia level; and   (c) if the fasting plasma ammonia level is greater than half the upper limit of normal for plasma ammonia level, administering an increased dosage of glyceryl tri-[4-phenylbutyrate].   
     
     
         20 . The method of  claim 19 , wherein the plasma sample is stored at ≦−18° C.