Methods of therapeutic monitoring of phenylacetic acid prodrugs

Abstract

The present disclosure provides methods for adjusting the dosage of PAA prodrugs (e.g., HPN-100, PBA) based on measurement of PAA and PAGN in plasma and calculating the PAA:PAGN ratio so as to determine whether PAA to PAGN conversion is saturated.

1 - 13 . (canceled) 
     
     
         14 . A method of treating a urea cycle disorder in a subject experiencing symptoms of nausea, headache, somnolence, or confusion, having a plasma ammonia level within normal limits, and having a plasma PAA to PAGN ratio exceeding 2.5, the method comprising:
 administering to said subject, a dosage of glyceryl tri-[4-phenylbutyrate] effective to achieve a plasma PAA to PAGN ratio below 2.5.   
     
     
         15 . The method of  claim 14 , wherein the subject has moderate hepatic impairment. 
     
     
         16 . The method of  claim 14 , wherein the subject has a low body surface area. 
     
     
         17 . The method of  claim 14 , wherein the dosage of glyceryl tri-[4-phenylbutyrate] is administered orally. 
     
     
         18 . The method of  claim 14 , further comprising measuring the plasma ammonia level of the subject.