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 predicting the maximum daily blood ammonia value for a patient in need thereof, consisting of:
 measuring the patient's fasting morning blood ammonia level,   wherein if the fasting morning blood ammonia level is less than or equal to half the upper limit of normal for blood ammonia for the laboratory which performed the fasting morning blood ammonia level measurement, the patient has an average likelihood of about 70% to 80% within a 95% confidence interval that the patient's maximum daily blood ammonia level will not exceed 1.5 times the upper limit of normal for blood ammonia.   
     
     
         13 . The method of  claim 12 , wherein the average likelihood is about 75% with 95% confidence that the true probability is between 58% and 86%. 
     
     
         14 . The method of  claim 12 , further comprising administering a therapeutically effective amount of glycerol triphenylbutyrate to said patient if the fasting morning blood ammonia level is greater than half the upper limit of normal. 
     
     
         15 . A method of predicting the maximum daily blood ammonia value for a patient in need thereof, consisting of:
 measuring the patient's fasting morning blood ammonia level,   wherein if the fasting morning blood ammonia level is less than or equal to half the upper limit of normal for blood ammonia for the laboratory which performed the fasting morning blood ammonia level measurement, the patient has an average likelihood of about 84% within a 95% confidence interval that the patient's maximum daily blood ammonia level will not exceed 1.5 times the upper limit of normal for blood ammonia.   
     
     
         16 . The method of  claim 15 , wherein the average likelihood is about 84% with 95% confidence that the true probability is between 65% and 93%. 
     
     
         17 . The method of  claim 15 , further comprising administering a therapeutically effective amount of glycerol triphenylbutyrate to said patient if the fasting morning blood ammonia level is greater than half the upper limit of normal. 
     
     
         18 . A method of predicting maximum daily blood ammonia level in a patient in need thereof, consisting of:
 measuring the patient's fasting morning blood ammonia level,   wherein if the fasting morning blood ammonia level is less than or equal to half the upper limit of normal for blood ammonia for the laboratory which performed the fasting morning blood ammonia level measurement, the patient has an average likelihood of 90% to 98% within a 95% confidence interval that the patient's maximum daily blood ammonia level will be less than 100 μmol/L.   
     
     
         19 . The method of  claim 18 , wherein the average likelihood is about 93% with 95% confidence that the true probability is between 77% and 100%. 
     
     
         20 . The method of  claim 18 , further comprising administering a therapeutically effective amount of glycerol triphenylbutyrate to said patient if the fasting morning blood ammonia level is greater than half the upper limit of normal.