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 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 by analyzing, a plasma sample from the subject that has been stored at 0-15° C.;
(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].
13 . The method of claim 12 , wherein the plasma sample is analyzed within 3 hours of collection.
14 . The method of claim 12 , wherein the plasma sample is analyzed within less than 1 hour of collection.
15 . The method of claim 12 , wherein the plasma sample is analyzed immediately after collection.
16 . 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.
17 . The method of claim 12 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L.
18 . The method of claim 12 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally.
19 . 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 by analyzing a plasma sample from the subject that has been stored at below 0° C.;
(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].
20 . The method of claim 19 , wherein the plasma sample is stored at ≦−18° C.