Claims for Patent: 9,962,359

Summary for Patent: 9,962,359

Title:	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.
Inventor(s):	Scharschmidt; Bruce (San Francisco, CA), Mokhtarani; Masoud (Walnut Creek, CA)
Assignee:	Horizon Therapeutics, LLC (Lake Forest, IL)
Application Number:	15/687,132
Patent Claims:	1. A method of treating a subject with a urea cycle disorder (UCD) who has a fasting morning plasma ammonia level less than the upper limit of normal and who is not experiencing a hyperammonemic crisis, wherein the UCD is chosen from OTC deficiency, CPS1 deficiency, ASS deficiency, and ASL deficiency, the method comprising: a) orally administering an initial dosage of glyceryl tri[4-phenylbutyrate]; b) after a time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady state, measuring a single fasting morning plasma ammonia level for the subject and not serial blood draws; c) comparing the fasting morning plasma ammonia level to the upper limit of normal, wherein the upper limit of normal is relative to the reference range of normal values at the laboratory in which the ammonia was measured; and d) orally administering an adjusted dosage of glyceryl tri-[4-phenylbutyrate], wherein the adjusted dosage is greater than the initial dosage if the fasting morning plasma ammonia level is greater than half the upper limit of normal for plasma ammonia level, wherein a subject with a fasting ammonia in the range 0-0.5 ULN has a greater than 80% likelihood of having an average daily ammonia level within a normal range. 2. The method of claim 1, wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady state is 48 hours. 3. The method of claim 1, wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady state is 48 to 72 hours. 4. The method of claim 1, wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady state is 72 hours to 1 week. 5. The method of claim 1, wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady state is 1 week to 2 weeks. 6. The method of claim 1, wherein the time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady state is greater than 2 weeks. 7. The method of claim 1, further comprising repeating steps (b) to (d) until the subject exhibits a fasting morning plasma ammonia level at or below half the upper limit of normal for plasma ammonia level. 8. The method of claim 1, wherein the upper limit of normal for plasma ammonia level is 35 .mu.mol/L. 9. The method of claim 1, wherein the fasting plasma ammonia level is measured from a fasting morning blood draw. 10. The method of claim 1, wherein the fasting period for obtaining a fasting blood ammonia level is overnight. 11. A method of treating a subject with a urea cycle disorder (UCD) who has a fasting plasma ammonia level less than the upper limit of normal and who is not experiencing a hyperammonemic crisis, wherein the UCD is chosen from OTC deficiency, CPS1 deficiency, ASS deficiency, and ASL deficiency, the method consisting of: a) orally administering an initial dosage of glyceryl tri-[4-phenylbutyrate]; b) after a time period sufficient for the glyceryl tri-[4-phenylbutyrate] to reach steady state, measuring a single fasting plasma ammonia level for the subject and not serial blood draws; c) comparing the fasting plasma ammonia level to the upper limit of normal, wherein the upper limit of normal is relative to the reference range of normal values at the laboratory in which the ammonia was measured; and d) orally 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, wherein a subject with a fasting ammonia in the range 0-0.5 ULN has a greater than 80% likelihood of having an average daily ammonia level within a normal range. 12. The method of claim 11, wherein the fasting plasma ammonia level is measured from a fasting morning blood draw. 13. The method of claim 11, wherein the fasting period for obtaining a fasting blood ammonia level is overnight.