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Quantitative impact of pre-analytical process on plasma uracil when testing for dihydropyrimidine dehydrogenase deficiency.
Maillard, Maud; Launay, Manon; Royer, Bernard; Guitton, Jérôme; Gautier-Veyret, Elodie; Broutin, Sophie; Tron, Camille; Le Louedec, Félicien; Ciccolini, Joseph; Richard, Damien; Alarcan, Hugo; Haufroid, Vincent; Tafzi, Naïma; Schmitt, Antonin; Etienne-Grimaldi, Marie-Christine; Narjoz, Céline; Thomas, Fabienne.
Afiliación
  • Maillard M; Laboratoire de Pharmacologie, Institut Claudius Regaud, IUCT-Oncopole et Centre de Recherches en Cancérologie de Toulouse, Inserm UMR1037, Université Paul Sabatier, Toulouse, France.
  • Launay M; Laboratoire de Pharmacologie et Toxicologie, CHU de Saint-Etienne, Saint-Etienne, France.
  • Royer B; Laboratoire de Pharmacologie Clinique et Toxicologie, CHU Besançon and Univ. Bourgogne Franche-Comté, INSERM, EFS BFC, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France.
  • Guitton J; Laboratoire de Pharmacologie Toxicologie, CHU de Lyon, Lyon, France.
  • Gautier-Veyret E; Laboratoire de Pharmacologie, Pharmacogénétique et Toxicologie, CHU Grenoble-Alpes et Université Grenoble-Alpes, laboratoire HP2, INSERM U1300, Grenoble, France.
  • Broutin S; Département de Biologie et Pathologie Médicale, Service de Pharmacologie, Gustave Roussy, Villejuif, France.
  • Tron C; Laboratoire de pharmacologie CHU de Rennes, Université de Rennes, CHU de Rennes, Inserm, EHESP, Irset (Institut de recherche en santé, environnement et travail), UMR_S 1085, Rennes, France.
  • Le Louedec F; Laboratoire de Pharmacologie, Institut Claudius Regaud, IUCT-Oncopole et Centre de Recherches en Cancérologie de Toulouse, Inserm UMR1037, Université Paul Sabatier, Toulouse, France.
  • Ciccolini J; SMARTc Unit, CRCM Inserm U1068 et Laboratoire de Pharmacocinétique, CHU La Timone, Marseille, France.
  • Richard D; Laboratoire de Pharmacologie et Toxicologie, CHU de Clermont-Ferrand, Clermont-Ferrand, France.
  • Alarcan H; Service de Biochimie et Biologie Moléculaire, CHRU de Tours, Tours, France.
  • Haufroid V; Louvain Centre for Toxicology and Applied Pharmacology (LTAP), Clinical and Experimental Research Institute (IREC), Université catholique de Louvain, Brussels, Belgium.
  • Tafzi N; Clinical Chemistry Department, Cliniques Universitaires Saint-Luc, Brussels, Belgium.
  • Schmitt A; INSERM, Université de Limoge, Service de Pharmacologie et Toxicologie, CHU de Limogess, U1248 IPPRITT, Limoges, France.
  • Etienne-Grimaldi MC; Service Pharmacie, Centre Georges-François Leclerc et INSERM U1231, Université de Bourgogne, Dijon, France.
  • Narjoz C; Laboratoire d'Oncopharmacologie, Centre Antoine Lacassagne, Nice, France.
  • Thomas F; Assistance Publique des Hôpitaux de Paris, Hôpital européen Georges-Pompidou, Service de biochimie, Paris, France.
Br J Clin Pharmacol ; 89(2): 762-772, 2023 02.
Article en En | MEDLINE | ID: mdl-36104927
AIMS: Determining dihydropyrimidine dehydrogenase (DPD) activity by measuring patient's uracil (U) plasma concentration is mandatory before fluoropyrimidine (FP) administration in France. In this study, we aimed to refine the pre-analytical recommendations for determining U and dihydrouracil (UH2 ) concentrations, as they are essential in reliable DPD-deficiency testing. METHODS: U and UH2 concentrations were collected from 14 hospital laboratories. Stability in whole blood and plasma after centrifugation, the type of anticoagulant and long-term plasma storage were evaluated. The variation induced by time and temperature was calculated and compared to an acceptability range of ±20%. Inter-occasion variability (IOV) of U and UH2 was assessed in 573 patients double sampled for DPD-deficiency testing. RESULTS: Storage of blood samples before centrifugation at room temperature (RT) should not exceed 1 h, whereas cold (+4°C) storage maintains the stability of uracil after 5 hours. For patients correctly double sampled, IOV of U reached 22.4% for U (SD = 17.9%, range = 0-99%). Notably, 17% of them were assigned with a different phenotype (normal or DPD-deficient) based on the analysis of their two samples. For those having at least one non-compliant sample, this percentage increased up to 33.8%. The moment of blood collection did not affect the DPD phenotyping result. CONCLUSION: Caution should be taken when interpreting U concentrations if the time before centrifugation exceeds 1 hour at RT, since it rises significantly afterwards. Not respecting the pre-analytical conditions for DPD phenotyping increases the risk of DPD status misclassification.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Deficiencia de Dihidropirimidina Deshidrogenasa Límite: Humans Idioma: En Revista: Br J Clin Pharmacol Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Deficiencia de Dihidropirimidina Deshidrogenasa Límite: Humans Idioma: En Revista: Br J Clin Pharmacol Año: 2023 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido