Switching to Glycerol Phenylbutyrate in 48 Patients with Urea Cycle Disorders: Clinical Experience in Spain

July 25, 2024

Publications

>

Article

Sí

Publicated to: Journal Of Clinical Medicine. 11 (17): 5045- - 2022-09-01 11(17), DOI: 10.3390/jcm11175045

Authors: Martín-Hernández, E; Quijada-Fraile, P; Correcher, P; Meavilla, S; Sánchez-Pintos, P; Montero, JD; Blasco-Alonso, J; Dougherty, L; Marquez, A; Peña-Quintana, L; Cañedo, E; García-Jimenez, MC; Lozano, PJM; Hurtado, MM; Gómez, MC; Barrio-Carreras, D; de los Santos, M; del Toro, M; Couce, ML; Miñana, IV; Conejo, MM; Bellusci, M

Affiliations

Biocruces Bizkaia Hlth Res Inst - Author

Complejo Hosp Univ Canarias, Secc Nutr & Errores Innatos Metab, Pediat - Author

Hosp Badajoz, Unidad Gastroenterol & Enfermedades Metab - Author

Hosp Clin Barcelona, Dept Med Interna, Unidad Enfermedades Musculares & Metab Hereditari - Author

Hosp Clin Univ Santiago de Compostela, CIBERER, Europeo MetabERN Enfermedades Metab, IDIS - Author

Hosp La Fe Valencia, Ctr Referencia Nacl Enfermedades Metab CSUR - Author

Hosp Miguel Servet, Unidad Metab - Author

Hosp Nino Jesus, Unidad Gastroenterol & Nutr - Author

Hosp Reg Univ Malaga, Grp IBIMA Multidisciplinar Pediat, Unidad Enfermedades Metab Hereditarias, Secc Gastroenterol & Nutr Infantil - Author

Hosp San Joan Deu Barcelona, Europeo MetabERN Enfermedades Metab - Author

Hosp Univ 12 Octubre, Europeo MetabERN Enfermedades Metab, Inst Invest I 12, CIBERER - Author

Hosp Valle De Hebron, Europeo MetabERN Enfermedades Metab - Author

Univ Las Palmas Gran Canaria, Unidad Gastroenterol & Nutr Pediat, Complejo Hosp Univ Insular Materno Infantil Palma, CIBEROBN,ISCIII,ACIP - Author

Abstract

Background and objectives: Glycerol phenylbutyrate (GPB) has demonstrated safety and efficacy in patients with urea cycle disorders (UCDs) by means of its clinical trial program, but there are limited data in clinical practice. In order to analyze the efficacy and safety of GPB in clinical practice, here we present a national Spanish experience after direct switching from another nitrogen scavenger to GPB. Methods: This observational, retrospective, multicenter study was performed in 48 UCD patients (age 11.7 +/- 8.2 years) switching to GPB in 13 centers from nine Spanish regions. Clinical, biochemical, and nutritional data were collected at three different times: prior to GPB introduction, at first follow-up assessment, and after one year of GPB treatment. Number of related adverse effects and hyperammonemic crisis 12 months before and after GPB introduction were recorded. Results: GPB was administered at a 247.8 +/- 102.1 mg/kg/day dose, compared to 262.6 +/- 126.1 mg/kg/day of previous scavenger (46/48 Na-phenylbutyrate). At first follow-up (79 +/- 59 days), a statistically significant reduction in ammonia (from 40.2 +/- 17.3 to 32.6 +/- 13.9 mu mol/L, p < 0.001) and glutamine levels (from 791.4 +/- 289.8 to 648.6 +/- 247.41 mu mol/L, p < 0.001) was observed. After one year of GPB treatment (411 +/- 92 days), we observed an improved metabolic control (maintenance of ammonia and glutamine reduction, with improved branched chain amino acids profile), and a reduction in hyperammonemic crisis rate (from 0.3 +/- 0.7 to less than 0.1 +/- 0.3 crisis/patients/year, p = 0.02) and related adverse effects (RAE, from 0.5 to less than 0.1 RAEs/patients/year p < 0.001). Conclusions: This study demonstrates the safety of direct switching from other nitrogen scavengers to GPB in clinical practice, which improves efficacy, metabolic control, and RAE compared to previous treatments.

Keywords

clinical practiceglycerol phenylbutyrate (gpb)sodium benzoate (nabz)sodium phenylbutyrate (napb)Ammonia controlBiomarkerChildrenClinical practiceEfficacyGlutamineGlycerol phenylbutyrate (gpb)Hyperammonemic crisesPediatric-patientsSafetySodium benzoate (nabz)Sodium phenylbutyrateSodium phenylbutyrate (napb)Urea cycle disorders (ucds)Urinary phenylacetylglutamine

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Clinical Medicine due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous).

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.09. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-12-06, the following number of citations:

WoS: 8
Europe PMC: 3

Indexed in

License and Use

Citations

Altmetrics

Analysis of institutional authors

Share