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;
(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], wherein administering said increased dosage comprises increasing the amount of glyceryl tri-[4-phenylbutyrate]per administration.
13 . The method of claim 12 , wherein the amount of glyceryl tri-[4-phenylbutyrate] is increased from a 3 mL dosage to a 6 mL dosage.
14 . 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.
15 . The method of claim 12 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L.
16 . The method of claim 12 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally.
17 . 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;
(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], wherein administering said increased dosage comprises increasing the number of administrations of glyceryl tri-[4-phenylbutyrate] per day.
18 . The method of claim 17 , 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.
19 . The method of claim 17 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L.
20 . The method of claim 17 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally.
21 . The method of claim 17 , wherein the number of administrations is increased from once-a-day dosing to twice-a-day dosing.
22 . The method of claim 17 , wherein the number of administrations is increased from once-a-day dosing to three times-a-day dosing.
23 . 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;
(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], wherein administering said increased dosage comprises increasing the number of administrations of glyceryl tri-[4-phenylbutyrate]per day and the amount of glyceryl tri-[4-phenylbutyrate]per administration.
24 . The method of claim 23 , 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.
25 . The method of claim 23 , wherein the upper limit of normal for plasma ammonia level is 35 μmol/L.
26 . The method of claim 23 , wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally.