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Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?

Tacrolimus presents high intra and inter-individual variability in its blood trough concentration (Cmin). Knowledge of the factors that are involved in tacrolimus Cmin variability is thus clinically important to prevent or limit it. Inflammation can affect the pharmacokinetic properties of drugs. We...

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Autores principales: Chavant, Anaelle, Fonrose, Xavier, Gautier-Veyret, Elodie, Hilleret, Marie Noelle, Roustit, Matthieu, Stanke-Labesque, Francoise
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623792/
https://www.ncbi.nlm.nih.gov/pubmed/34834375
http://dx.doi.org/10.3390/pharmaceutics13111960
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author Chavant, Anaelle
Fonrose, Xavier
Gautier-Veyret, Elodie
Hilleret, Marie Noelle
Roustit, Matthieu
Stanke-Labesque, Francoise
author_facet Chavant, Anaelle
Fonrose, Xavier
Gautier-Veyret, Elodie
Hilleret, Marie Noelle
Roustit, Matthieu
Stanke-Labesque, Francoise
author_sort Chavant, Anaelle
collection PubMed
description Tacrolimus presents high intra and inter-individual variability in its blood trough concentration (Cmin). Knowledge of the factors that are involved in tacrolimus Cmin variability is thus clinically important to prevent or limit it. Inflammation can affect the pharmacokinetic properties of drugs. We evaluated the contribution of acute inflammation in the pharmacokinetic variability of tacrolimus blood Cmin in a large cohort of liver transplant patients. Demographic, biological, and clinical data from 248 liver transplant patients treated with tacrolimus from January 2010 to December 2016 were retrospectively collected from medical records. In total, 1573 Cmin/dose and concomitant C-reactive protein (CRP) measurements were analysed. In multivariate analysis, the log Cmin/dose of tacrolimus was significantly and positively associated with the hematocrit, ALAT, and CRP concentrations. CRP concentrations were higher (p = 0.003) for patients with tacrolimus overexposure (i.e., tacrolimus Cmin > 15 µg/L) (median CRP (10th–90th percentiles): 27 mg/L (3–149 mg/L), n = 91) than they were for patients with a tacrolimus Cmin ≤ 15 µg/L (13 mg/mL (3–95 mg/L), n = 1482)). CRP in the fourth quartile (49 to 334 mg/L) was associated with a 2.6-fold increased risk of tacrolimus Cmin overexposure. Our study provides evidence that inflammation contributes to tacrolimus Cmin variability and suggests that inflammation should be considered for the correct interpretation of tacrolimus blood concentration.
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spelling pubmed-86237922021-11-27 Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation? Chavant, Anaelle Fonrose, Xavier Gautier-Veyret, Elodie Hilleret, Marie Noelle Roustit, Matthieu Stanke-Labesque, Francoise Pharmaceutics Article Tacrolimus presents high intra and inter-individual variability in its blood trough concentration (Cmin). Knowledge of the factors that are involved in tacrolimus Cmin variability is thus clinically important to prevent or limit it. Inflammation can affect the pharmacokinetic properties of drugs. We evaluated the contribution of acute inflammation in the pharmacokinetic variability of tacrolimus blood Cmin in a large cohort of liver transplant patients. Demographic, biological, and clinical data from 248 liver transplant patients treated with tacrolimus from January 2010 to December 2016 were retrospectively collected from medical records. In total, 1573 Cmin/dose and concomitant C-reactive protein (CRP) measurements were analysed. In multivariate analysis, the log Cmin/dose of tacrolimus was significantly and positively associated with the hematocrit, ALAT, and CRP concentrations. CRP concentrations were higher (p = 0.003) for patients with tacrolimus overexposure (i.e., tacrolimus Cmin > 15 µg/L) (median CRP (10th–90th percentiles): 27 mg/L (3–149 mg/L), n = 91) than they were for patients with a tacrolimus Cmin ≤ 15 µg/L (13 mg/mL (3–95 mg/L), n = 1482)). CRP in the fourth quartile (49 to 334 mg/L) was associated with a 2.6-fold increased risk of tacrolimus Cmin overexposure. Our study provides evidence that inflammation contributes to tacrolimus Cmin variability and suggests that inflammation should be considered for the correct interpretation of tacrolimus blood concentration. MDPI 2021-11-19 /pmc/articles/PMC8623792/ /pubmed/34834375 http://dx.doi.org/10.3390/pharmaceutics13111960 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
Chavant, Anaelle
Fonrose, Xavier
Gautier-Veyret, Elodie
Hilleret, Marie Noelle
Roustit, Matthieu
Stanke-Labesque, Francoise
Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?
title Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?
title_full Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?
title_fullStr Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?
title_full_unstemmed Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?
title_short Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?
title_sort variability of tacrolimus trough concentration in liver transplant patients: which role of inflammation?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623792/
https://www.ncbi.nlm.nih.gov/pubmed/34834375
http://dx.doi.org/10.3390/pharmaceutics13111960
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