Ammonia Control in Children Ages 2 Months through 5 Years with Urea Cycle Disorders: Comparison of Sodium Phenylbutyrate and Glycerol Phenylbutyrate - 23/05/13
, George A. Diaz, MD, PhD 2, Uta Lichter-Konecki, MD, PhD 3, Susan A. Berry, MD 4, Cary O. Harding, MD 5, Shawn E. McCandless, MD 6, Cindy LeMons 7, Joe Mauney, MS 8, Klara Dickinson, BS 9, Dion F. Coakley, PharmD 9, Tristen Moors, MS 9, Masoud Mokhtarani, MD 9, Bruce F. Scharschmidt, MD 9, Brendan Lee, MD, PhD 10, 11
Reprint requests: Wendy Smith, MD, Division of Genetics, Pediatric Specialty Care, The Barbara Bush Children’s Hospital, 1577 Congress St, Portland, ME 04102.Abstract |
Objectives |
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).
Study design |
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.
Le texte complet de cet article est disponible en PDF.Keyword : ASA, ASL, ASS, AUC0-24, DSMB, G tube, GPB, NaPBA, NH324-hour AUC, PAA, PAGN, PBA, PK, UCD, U-PAGN
Plan
| Financial support, conflicts of interest, trial registration, and poster presentation information is available at www.jpeds.com (Appendix). |
Vol 162 - N° 6
P. 1228 - juin 2013 Retour au numéro
Article précédent
- Fluticasone Propionate Pharmacogenetics: CYP3A4*22 Polymorphism and Pediatric Asthma Control
- Chris Stockmann, Bernhard Fassl, Roger Gaedigk, Flory Nkoy, Derek A. Uchida, Steven Monson, Christopher A. Reilly, J. Steven Leeder, Garold S. Yost, Robert M. Ward
- Endocrine Evaluation of Children with and without Shwachman-Bodian-Diamond Syndrome Gene Mutations and Shwachman-Diamond Syndrome
- Kasiani C. Myers, Susan R. Rose, Meilan M. Rutter, Parinda A. Mehta, Jane C. Khoury, Theresa Cole, Richard E. Harris
Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.
Déjà abonné à cette revue ?