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 ammonia exposure for a patient having a urea cycle disorder (UCD) comprising measuring a fasting blood ammonia level for the subject wherein increasing fasting ammonia being associated with higher AUC 0-24 hr  and maximum observed ammonia. 
     
     
         13 . The method of  claim 12 , wherein ammonia exposure is chosen from daily ammonia burden, average daily ammonia level, and/or highest daily ammonia value. 
     
     
         14 . The method of  claim 12 , wherein the blood sample used for measuring fasting blood ammonia levels is a venous blood sample. 
     
     
         15 . The method of  claim 12 , wherein the blood sample used for measuring fasting blood ammonia levels is a plasma blood sample. 
     
     
         16 . The method of  claim 12 , wherein the fasting blood ammonia level is measured from a fasting morning blood draw. 
     
     
         17 . The method of  claim 12 , wherein the fasting period for obtaining a fasting blood ammonia level is 4 hours or more, 5 hours or more, 6 hours or more, 7 hours or more, 8 hours or more, 9 hours or more, 10 hours or more, 11 hours or more, or 12 hours or more. 
     
     
         18 . The method of  claim 12 , wherein the fasting period for obtaining a fasting blood ammonia level is 4-8 hours, 6-8 hours, or 8-12 hours. 
     
     
         19 . The method of  claim 12 , wherein the fasting period for obtaining a fasting blood ammonia level is overnight. 
     
     
         20 . The method of  claim 12 , wherein the upper limit of normal for blood ammonia level is 35 μmol/L. 
     
     
         21 . The method of  claim 12 , further comprising comparing the fasting blood ammonia level for the subject with the upper limit of normal for the laboratory. 
     
     
         22 . A kit for determining whether to administer or adjust the dosage of a nitrogen scavenging drug for a subject with a nitrogen retention disorder, wherein the kit comprises:
 one or more nitrogen scavenging drugs;   one or more reagents or enzymes to measure blood ammonia levels in a sample; and   optionally other pigments, binders, surfactants, buffers, stabilizers, and/or chemicals necessary to obtain a blood sample and to measure the ammonia level in the sample.   
     
     
         23 . The kit of  claim 22 , wherein the one or more reagents comprises bromophenol blue. 
     
     
         24 . The kit of  claim 22 , wherein the one or more enzymes includes glutamate dehydrogenase.