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Monitoring Tacrolimus Concentrations in Whole Blood and Peripheral Blood Mononuclear Cells: Inter- and Intra-Patient Variability in a Cohort of Pediatric Patients.
De Nicolò, Amedeo; Pinon, Michele; Palermiti, Alice; Nonnato, Antonello; Manca, Alessandra; Mula, Jacopo; Catalano, Silvia; Tandoi, Francesco; Romagnoli, Renato; D'Avolio, Antonio; Calvo, Pier Luigi.
Afiliación
  • De Nicolò A; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Turin, Italy.
  • Pinon M; Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy.
  • Palermiti A; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Turin, Italy.
  • Nonnato A; Clinical Biochemistry Unit, Department of Diagnostic Laboratory, A.O.U. Città della Salute e della Scienza Hospital, Turin, Italy.
  • Manca A; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Turin, Italy.
  • Mula J; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Turin, Italy.
  • Catalano S; General Surgery, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
  • Tandoi F; General Surgery, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
  • Romagnoli R; General Surgery, Liver Transplant Center, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy.
  • D'Avolio A; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Turin, Italy.
  • Calvo PL; Pediatric Gastroenterology Unit, Regina Margherita Children's Hospital, Azienda Ospedaliera-Universitaria Città della Salute e della Scienza, Turin, Italy.
Front Pharmacol ; 12: 750433, 2021.
Article en En | MEDLINE | ID: mdl-34803692
Tacrolimus (TAC) is a first-choice immunosuppressant for solid organ transplantation, characterized by high potential for drug-drug interactions, significant inter- and intra-patient variability, and narrow therapeutic index. Therapeutic drug monitoring (TDM) of TAC concentrations in whole blood (WB) is capable of reducing the incidence of adverse events. Since TAC acts within lymphocytes, its monitoring in peripheral blood mononuclear cells (PBMC) may represent a valid future alternative for TDM. Nevertheless, TAC intracellular concentrations and their variability are poorly described, particularly in the pediatric context. Therefore, our aim was describing TAC concentrations in WB and PBMC and their variability in a cohort of pediatric patients undergoing constant immunosuppressive maintenance therapy, after liver transplantation. TAC intra-PBMCs quantification was performed through a validated UHPLC-MS/MS assay over a period of 2-3 months. There were 27 patients included in this study. No significant TAC changes in intracellular concentrations were observed (p = 0.710), with a median percent change of -0.1% (IQR -22.4%-+46.9%) between timings: this intra-individual variability was similar to the one in WB, -2.9% (IQR -29.4-+42.1; p = 0.902). Among different patients, TAC weight-adjusted dose and age appeared to be significant predictors of TAC concentrations in WB and PBMC. Intra-individual seasonal variation of TAC concentrations in WB, but not in PBMC, have been observed. These data show that the intra-individual variability in TAC intracellular exposure is comparable to the one observed in WB. This opens the way for further studies aiming at the identification of therapeutic ranges for TAC intra-PBMC concentrations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: Front Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Risk_factors_studies Idioma: En Revista: Front Pharmacol Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Suiza