Urinary phenylacetylglutamine (U-PAGN) concentration as biomarker for adherence in patients with urea cycle disorders (UCD) treated with glycerol phenylbutyrate

M Mokhtarani; G A Diaz; U Lichter-Konecki; S A Berry; J Bartley; S E McCandless; W Smith; C Harding; C Le Mons; D F Coakley; B Lee; B F Scharschmidt

doi:10.1016/j.ymgmr.2015.09.003

Urinary phenylacetylglutamine (U-PAGN) concentration as biomarker for adherence in patients with urea cycle disorders (UCD) treated with glycerol phenylbutyrate

Mol Genet Metab Rep. 2015 Sep 27:5:12-14. doi: 10.1016/j.ymgmr.2015.09.003. eCollection 2015 Dec.

Authors

M Mokhtarani¹, G A Diaz², U Lichter-Konecki³, S A Berry⁴, J Bartley⁵, S E McCandless⁶, W Smith⁷, C Harding⁸, C Le Mons⁹, D F Coakley¹, B Lee¹⁰, B F Scharschmidt¹

Affiliations

¹ Horizon Pharma, Brisbane, CA, USA.
² Mount Sinai School of Medicine, New York, NY, USA.
³ Drexel University, Philadelphia, PA, USA.
⁴ University of Minnesota, Minneapolis, MN, USA.
⁵ Long Beach Memorial Hospital, Long Beach, CA, USA.
⁶ Case Western Reserve University, Cleveland, OH, USA.
⁷ Maine Medical Center, Portland, ME, USA.
⁸ Oregon Health & Science University, Portland, OR, USA.
⁹ National Urea Cycle Disorders Foundation, Pasadena, CA, USA.
¹⁰ Baylor College of Medicine, Houston, TX, USA.

Abstract

Urinary phenylacetylglutamine (U-PAGN) concentrations in spot urine samples were analyzed as a dosing biomarker during glycerol phenylbutyrate (GPB) dosing in 68 healthy adults and 66 adult and pediatric patients with urea cycle disorders who participated in GPB clinical trials. Age- and body surface area (BSA)-specific 25th percentile cutoff points for spot U-PAGN concentrations (<~9000 μg/mL for < 2 years old patients, < 7000 μg/mL for > 2 years with BSA ≤ 1.3 m², and <~5000 μg/mL for > 2 years of age with BSA > 1.3 m²) were determined as an approach to identify patients for whom increased dosing and/or adherence to prescribed dosing should be assessed.

Keywords: Biomarker; Glycerol phenylbutyrate; Phenylacetate; Phenylbutyrate; Urea cycle disorder; Urinary phenylacetylglutamine.