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 treating a subject with a urea cycle disorder who has a fasting plasma ammonia level less than the upper limit of normal for plasma ammonia level, the method comprising:
(a) administering an initial dosage of glyceryl tri-[4-phenylbutyrate];
(b) after a time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady study, measuring a fasting plasma ammonia level for the subject;
(c) comparing the fasting plasma ammonia level to the upper limit of normal for plasma ammonia level; and
(d) 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 , wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady study is 48 hours.
14 . The method of claim 1 , wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady study is 48 to 72 hours.
15 . The method of claim 12 , wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady study is 72 hours to 1 week.
16 . The method of claim 12 , wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady study is 1 week to 2 weeks.
17 . The method of claim 12 , wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady study is greater than 2 weeks.
18 . The method of claim 12 , further comprising repeating steps (b) to (d) 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 12 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L.
20 . The method of claim 12 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally.