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 no residual urea synthetic capacity, 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;   (b) comparing the fasting plasma ammonia level to the upper limit of normal for plasma ammonia level; and   (c) administering an adjusted dosage of glyceryl tri-[4-phenylbutyrate], wherein the adjusted dosage is greater than the initial dosage if the fasting plasma ammonia level is greater than half the upper limit of normal for plasma ammonia level.   
     
     
         13 . 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. 
     
     
         14 . The method of  claim 12 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L. 
     
     
         15 . The method of  claim 12 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally. 
     
     
         16 . A method of treating a subject with a urea cycle disorder who has residual urea synthetic capacity, 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;   (b) comparing the fasting plasma ammonia level to the upper limit of normal for plasma ammonia level; and   (c) administering an adjusted dosage of glyceryl tri-[4-phenylbutyrate], wherein the adjusted dosage is greater than the initial dosage if the fasting plasma ammonia level is greater than half the upper limit of normal for plasma ammonia level.   
     
     
         17 . The method of  claim 16 , 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. 
     
     
         18 . The method of  claim 16 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L. 
     
     
         19 . The method of  claim 16 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally.