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;   (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], wherein administering said increased dosage comprises increasing the amount of glyceryl tri-[4-phenylbutyrate]per administration.   
     
     
         13 . The method of  claim 12 , wherein the amount of glyceryl tri-[4-phenylbutyrate] is increased from a 3 mL dosage to a 6 mL dosage. 
     
     
         14 . 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. 
     
     
         15 . The method of  claim 12 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L. 
     
     
         16 . The method of  claim 12 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally. 
     
     
         17 . 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;   (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], wherein administering said increased dosage comprises increasing the number of administrations of glyceryl tri-[4-phenylbutyrate] per day.   
     
     
         18 . The method of  claim 17 , 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. 
     
     
         19 . The method of  claim 17 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L. 
     
     
         20 . The method of  claim 17 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally. 
     
     
         21 . The method of  claim 17 , wherein the number of administrations is increased from once-a-day dosing to twice-a-day dosing. 
     
     
         22 . The method of  claim 17 , wherein the number of administrations is increased from once-a-day dosing to three times-a-day dosing. 
     
     
         23 . 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;   (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], wherein administering said increased dosage comprises increasing the number of administrations of glyceryl tri-[4-phenylbutyrate]per day and the amount of glyceryl tri-[4-phenylbutyrate]per administration.   
     
     
         24 . The method of  claim 23 , 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. 
     
     
         25 . The method of  claim 23 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L. 
     
     
         26 . The method of  claim 23 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally.