title: Ammonia control in children ages 2 months through 5 years with urea cycle disorders: comparison of sodium phenylbutyrate and glycerol phenylbutyrate.
abstract: OBJECTIVE
  To examine ammonia levels, pharmacokinetics, and safety of glycerol phenylbutyrate (GPB; also referred to as HPN-100) and sodium phenylbutyrate (NaPBA) in young children with urea cycle disorders (UCDs).
  
  
  METHODS
  This open label switch-over study enrolled patients ages 29 days to under 6 years taking NaPBA. Patients underwent 24-hour blood and urine sampling on NaPBA and again on a phenylbutyric acid-equimolar dose of GPB and completed questionnaires regarding signs and symptoms associated with NaPBA and/or their UCD.
  
  
  RESULTS
  Fifteen patients (8 argininosuccinate lyase deficiency, 3 argininosuccinic acid synthetase deficiency, 3 ornithine transcarbamylase deficiency, 1 arginase deficiency) ages 2 months through 5 years enrolled in and completed the study. Daily ammonia exposure (24-hour area under the curve) was lower on GPB and met predefined noninferiority criteria (ratio of means 0.79; 95% CI 0.593-1.055; P=.03 Wilcoxon; 0.07 t test). Six patients experienced mild adverse events on GPB; there were no serious adverse events or significant laboratory changes. Liver tests and argininosuccinic acid levels among patients with argininosuccinate lyase deficiency were unchanged or improved on GPB. Eleven of 15 patients reported 35 symptoms on day 1; 23 of these 35 symptoms improved or resolved on GPB. Mean systemic exposure to phenylbutyric acid, phenylacetic acid, and phenylacetylglutamine (PAGN) were similar and phenylacetic acid exposure tended to be higher in the youngest children on both drugs. Urinary PAGN concentration was greater on morning voids and varied less over 24 hours on GPB versus NaPBA.
  
  
  CONCLUSIONS
  GPB results in more evenly distributed urinary output of PAGN over 24 hours were associated with fewer symptoms and offers ammonia control comparable with that observed with NaPBA in young children with UCDs.
authors: Division of Genetics, Department of Pediatrics, Maine Medical Center, Portland, ME 04102, USA. SMITHW@mmc.org
authors: Wendy
authors: W
authors: Smith
authors: George A
authors: GA
authors: Diaz
authors: Uta
authors: U
authors: Lichter-Konecki
authors: Susan A
authors: SA
authors: Berry
authors: Cary O
authors: CO
authors: Harding
authors: Shawn E
authors: SE
authors: McCandless
authors: Cindy
authors: C
authors: LeMons
authors: Joe
authors: J
authors: Mauney
authors: Klara
authors: K
authors: Dickinson
authors: Dion F
authors: DF
authors: Coakley
authors: Tristen
authors: T
authors: Moors
authors: Masoud
authors: M
authors: Mokhtarani
authors: Bruce F
authors: BF
authors: Scharschmidt
authors: Brendan
authors: B
authors: Lee
mesh_terms: D000641:Ammonia / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D057915:Drug Substitution; D005260:Female; D005973:Glutamine / Q000031:analogs & derivatives / Q000652:urine; D005990:Glycerol / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D007223:Infant; D008099:Liver / Q000503:physiopathology*; D008297:Male; D010654:Phenylbutyrates / Q000008:administration & dosage* / Q000009:adverse effects; D011795:Surveys and Questionnaires; D056806:Urea Cycle Disorders, Inborn / Q000097:blood / Q000188:drug therapy* / Q000652:urine
chemical_list: D010654:Phenylbutyrates; D005973:Glutamine; D000641:Ammonia; C075773:4-phenylbutyric acid; C003089:phenylacetylglutamine; D005990:Glycerol; C570223:glycerol phenylbutyrate