METHODS OF THERAPEUTIC MONITORING OF NITROGEN SCAVENGING DRUGS
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.