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Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study

Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observat...

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Autores principales: Pallio, Giovanni, Irrera, Natasha, Bitto, Alessandra, Mannino, Federica, Minutoli, Letteria, Rottura, Michelangelo, Pallio, Socrate, Altavilla, Domenica, Alibrandi, Angela, Marciano, Maria Concetta, Righi, Maria, Mannucci, Carmen, Arcoraci, Vincenzo, Squadrito, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354451/
https://www.ncbi.nlm.nih.gov/pubmed/32492825
http://dx.doi.org/10.3390/jpm10020047
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author Pallio, Giovanni
Irrera, Natasha
Bitto, Alessandra
Mannino, Federica
Minutoli, Letteria
Rottura, Michelangelo
Pallio, Socrate
Altavilla, Domenica
Alibrandi, Angela
Marciano, Maria Concetta
Righi, Maria
Mannucci, Carmen
Arcoraci, Vincenzo
Squadrito, Francesco
author_facet Pallio, Giovanni
Irrera, Natasha
Bitto, Alessandra
Mannino, Federica
Minutoli, Letteria
Rottura, Michelangelo
Pallio, Socrate
Altavilla, Domenica
Alibrandi, Angela
Marciano, Maria Concetta
Righi, Maria
Mannucci, Carmen
Arcoraci, Vincenzo
Squadrito, Francesco
author_sort Pallio, Giovanni
collection PubMed
description Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observation in 75 transplanted patients and to investigate if tacrolimus blood levels correlate with presence of genetic polymorphisms, thus modifying tacrolimus pharmacokinetics. CYP3A5*1 (G6986A), CYP3A4*1B (A392G), CYP3A4*22, ABCB1 (C3435T; C1236T; G2677A/T), SLCO1B1 (T521C), polymorphisms were analyzed. Based on the effect of their genotypes, patients were stratified into 5 groups: (1) reduced tacrolimus metabolism (RM), (2) increased metabolism (IM), (3) transporters polymorphisms (TM), (4) metabolism and transporter polymorphisms (AM) and (5) no mutations (Wild Type, WT). The percentage of the samples out of therapeutic range was significantly higher in the IM group than in the WT group (p = 0.001), as well as compared to the TM group (p = 0.004). Only IM pattern (p = 0.015) resulted as an independent predictor of number of tacrolimus blood levels out of therapeutic range. RM pattern (p = 0.006) was inversely related to the administered dose. Therefore, genotyping could become a standard practice before tacrolimus prescription thus decreasing side effects, increasing efficacy and reducing the economic burden for the national health system.
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spelling pubmed-73544512020-08-05 Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study Pallio, Giovanni Irrera, Natasha Bitto, Alessandra Mannino, Federica Minutoli, Letteria Rottura, Michelangelo Pallio, Socrate Altavilla, Domenica Alibrandi, Angela Marciano, Maria Concetta Righi, Maria Mannucci, Carmen Arcoraci, Vincenzo Squadrito, Francesco J Pers Med Article Precise tacrolimus treatment in transplanted patients is achieved in the clinical setting by performing therapeutic drug monitoring (TDM) and consequently adjusting therapy. The aim of this study was to retrospectively analyze the variability in tacrolimus blood levels throughout 2 years of observation in 75 transplanted patients and to investigate if tacrolimus blood levels correlate with presence of genetic polymorphisms, thus modifying tacrolimus pharmacokinetics. CYP3A5*1 (G6986A), CYP3A4*1B (A392G), CYP3A4*22, ABCB1 (C3435T; C1236T; G2677A/T), SLCO1B1 (T521C), polymorphisms were analyzed. Based on the effect of their genotypes, patients were stratified into 5 groups: (1) reduced tacrolimus metabolism (RM), (2) increased metabolism (IM), (3) transporters polymorphisms (TM), (4) metabolism and transporter polymorphisms (AM) and (5) no mutations (Wild Type, WT). The percentage of the samples out of therapeutic range was significantly higher in the IM group than in the WT group (p = 0.001), as well as compared to the TM group (p = 0.004). Only IM pattern (p = 0.015) resulted as an independent predictor of number of tacrolimus blood levels out of therapeutic range. RM pattern (p = 0.006) was inversely related to the administered dose. Therefore, genotyping could become a standard practice before tacrolimus prescription thus decreasing side effects, increasing efficacy and reducing the economic burden for the national health system. MDPI 2020-06-01 /pmc/articles/PMC7354451/ /pubmed/32492825 http://dx.doi.org/10.3390/jpm10020047 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pallio, Giovanni
Irrera, Natasha
Bitto, Alessandra
Mannino, Federica
Minutoli, Letteria
Rottura, Michelangelo
Pallio, Socrate
Altavilla, Domenica
Alibrandi, Angela
Marciano, Maria Concetta
Righi, Maria
Mannucci, Carmen
Arcoraci, Vincenzo
Squadrito, Francesco
Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study
title Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study
title_full Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study
title_fullStr Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study
title_full_unstemmed Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study
title_short Failure of Achieving Tacrolimus Target Blood Concentration Might Be Avoided by a Wide Genotyping of Transplanted Patients: Evidence from a Retrospective Study
title_sort failure of achieving tacrolimus target blood concentration might be avoided by a wide genotyping of transplanted patients: evidence from a retrospective study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354451/
https://www.ncbi.nlm.nih.gov/pubmed/32492825
http://dx.doi.org/10.3390/jpm10020047
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