METHODS OF THERAPEUTIC MONITORING OF NITROGEN SCAVENGING DRUGS

• US 20150335605A1
• Filed: 08/03/2015
• Published: 11/26/2015
• Est. Priority Date: 09/30/2011
• Status: Active Grant

• Current Assignee: Horizon Therapeutics, LLC (Amgen Inc.)
• Original Assignee: Horizon Therapeutics, Inc. (Amgen Inc.)
• Inventors: Scharschmidt, Bruce, Mokhtarani, Masoud
• Granted Patent: US 9,254,278 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/216 of acids having aromatic rings, e.g. benactizyne, clofibrate
• CPC Class Codes: A61K 31/235 having an aromatic ring attached to a carboxyl group
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 39/02 Antidotes
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: G01N 2800/04 Endocrine or metabolic disorders
• CPC Class Codes: G01N 2800/085 Liver diseases, e.g. portal hypertension, fibrosis, cirrhosis, bilirubin
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 31/221 for investigating pH value
• CPC Class Codes: G01N 33/4925 measuring blood gas content, e.g. O2, CO2 , HCO3
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH
• CPC Class Codes: Y10T 436/175383 Ammonia

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.

Claims

1-11. -11. (canceled)

12. A method of treating a subject with a urea cycle disorder, the method comprising:

administering to the subject in need thereof glyceryl tri-[4-phenylbutyrate] in an amount sufficient to produce a fasting plasma ammonia level that is less than half the upper limit of normal for plasma ammonia level.

13. The method of claim 12, wherein the upper limit of normal for plasma ammonia level is 35 μ

mol/L.

14. The method of claim 12, wherein the adjusted dosage of glyceryl tri-[4-phenylbutyrate] is administered orally.