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Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy
Tacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentration...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538499/ https://www.ncbi.nlm.nih.gov/pubmed/34683869 http://dx.doi.org/10.3390/pharmaceutics13101576 |
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author | Bodnar-Broniarczyk, Magdalena Durlik, Magdalena Bączkowska, Teresa Czerwińska, Katarzyna Marszałek, Ryszard Pawiński, Tomasz |
author_facet | Bodnar-Broniarczyk, Magdalena Durlik, Magdalena Bączkowska, Teresa Czerwińska, Katarzyna Marszałek, Ryszard Pawiński, Tomasz |
author_sort | Bodnar-Broniarczyk, Magdalena |
collection | PubMed |
description | Tacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentrations can be a better predictor with regards to acute rejection episode than TAC concentration in whole blood. Therefore, the aim of the study was to assess the correlation between dosage, blood, hepatic and kidney tissue concentration of TAC measured by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and clinical outcomes in a larger cohort of 100 liver and renal adult transplant recipients. Dried biopsies were weighed, mechanically homogenized and then the samples were treated with a mixture of zinc sulfate—acetonitrile to perform protein precipitation. After centrifugation, the extraction with tert-butyl methyl ether was performed. The analytical range was proven for TAC tissue concentrations of 10–400 pg/mg. The accuracy and precision fell within the acceptance criteria for intraday as well as interday assay. There was no correlation between dosage, blood (C(0)) and tissue TAC concentrations. TAC concentrations determined in liver and kidney biopsies ranged from 8.5 pg/mg up to 160.0 pg/mg and from 7.1 pg/mg up to 215.7 pg/mg, respectively. To the best of our knowledge, this is the first LC-MS/MS method for kidney and liver tissue TAC monitoring using Tac(13)C,D(2) as the internal standard, which permits measuring tissue TAC concentrations as low as 10 pg/mg. |
format | Online Article Text |
id | pubmed-8538499 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85384992021-10-24 Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy Bodnar-Broniarczyk, Magdalena Durlik, Magdalena Bączkowska, Teresa Czerwińska, Katarzyna Marszałek, Ryszard Pawiński, Tomasz Pharmaceutics Article Tacrolimus (TAC) has a narrow therapeutic index and highly variable pharmacokinetic characteristics. Close monitoring of the TAC concentrations is required in order to avoid the risk of acute rejection or adverse drug reaction. The results in some studies indicate that inter-tissue TAC concentrations can be a better predictor with regards to acute rejection episode than TAC concentration in whole blood. Therefore, the aim of the study was to assess the correlation between dosage, blood, hepatic and kidney tissue concentration of TAC measured by a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) and clinical outcomes in a larger cohort of 100 liver and renal adult transplant recipients. Dried biopsies were weighed, mechanically homogenized and then the samples were treated with a mixture of zinc sulfate—acetonitrile to perform protein precipitation. After centrifugation, the extraction with tert-butyl methyl ether was performed. The analytical range was proven for TAC tissue concentrations of 10–400 pg/mg. The accuracy and precision fell within the acceptance criteria for intraday as well as interday assay. There was no correlation between dosage, blood (C(0)) and tissue TAC concentrations. TAC concentrations determined in liver and kidney biopsies ranged from 8.5 pg/mg up to 160.0 pg/mg and from 7.1 pg/mg up to 215.7 pg/mg, respectively. To the best of our knowledge, this is the first LC-MS/MS method for kidney and liver tissue TAC monitoring using Tac(13)C,D(2) as the internal standard, which permits measuring tissue TAC concentrations as low as 10 pg/mg. MDPI 2021-09-28 /pmc/articles/PMC8538499/ /pubmed/34683869 http://dx.doi.org/10.3390/pharmaceutics13101576 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bodnar-Broniarczyk, Magdalena Durlik, Magdalena Bączkowska, Teresa Czerwińska, Katarzyna Marszałek, Ryszard Pawiński, Tomasz Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
title | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
title_full | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
title_fullStr | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
title_full_unstemmed | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
title_short | Kidney and Liver Tissue Tacrolimus Concentrations in Adult Transplant Recipients—The Influence of the Whole Blood and Tissue Concentrations on Efficiency of Treatment during Immunosuppressive Therapy |
title_sort | kidney and liver tissue tacrolimus concentrations in adult transplant recipients—the influence of the whole blood and tissue concentrations on efficiency of treatment during immunosuppressive therapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538499/ https://www.ncbi.nlm.nih.gov/pubmed/34683869 http://dx.doi.org/10.3390/pharmaceutics13101576 |
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