METHODS OF TREATMENT USING AMMONIA-SCAVENGING DRUGS

摘要

The invention provides a method for determining a dose and schedule and making dose adjustments of PBA prodrugs used to treat nitrogen retention states, or ammonia accumulation disorders, by measuring urinary excretion of phenylacetylglutamine and/or total urinary nitrogen. The invention provides methods to select an appropriate dosage of a PBA prodrug based on the patient's dietary protein intake, or based on previous treatments administered to the patient. The methods are applicable to selecting or modifying a dosing regimen for a subject receiving an orally administered ammonia scavenging drug.

主权项

1. A method of treating a subject having a nitrogen retention disorder comprising (a) determining a target urinary phenylacetyl glutamine (PAGN) output based on a target nitrogen output; (b) calculating an effective initial dosage of a phenylacetic acid (PAA) prodrug selected from glyceryl tri-[4-phenylbutyrate] (HPN-100) and phenylbutyric acid (PBA) or a pharmaceutically acceptable salt of PBA, wherein the effective dosage of PAA prodrug is calculated based on a mean conversion of PAA prodrug to urinary PAGN of 60% to 75%; and (c) administering the effective initial dosage of PAA prodrug to the patient.