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:	Anaelle Chavant, Xavier Fonrose, Elodie Gautier-Veyret, Marie Noelle Hilleret, Matthieu Roustit, Francoise Stanke-Labesque
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	tacrolimus trough concentration variability inflammation Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/5758fa186e064237851bed4c06b1e063
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spelling	oai:doaj.org-article:5758fa186e064237851bed4c06b1e0632021-11-25T18:42:23ZVariability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?10.3390/pharmaceutics131119601999-4923https://doaj.org/article/5758fa186e064237851bed4c06b1e0632021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4923/13/11/1960https://doaj.org/toc/1999-4923Tacrolimus 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 (<i>p</i> = 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), <i>n</i> = 91) than they were for patients with a tacrolimus Cmin ≤ 15 µg/L (13 mg/mL (3–95 mg/L), <i>n</i> = 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.Anaelle ChavantXavier FonroseElodie Gautier-VeyretMarie Noelle HilleretMatthieu RoustitFrancoise Stanke-LabesqueMDPI AGarticletacrolimustrough concentrationvariabilityinflammationPharmacy and materia medicaRS1-441ENPharmaceutics, Vol 13, Iss 1960, p 1960 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	tacrolimus trough concentration variability inflammation Pharmacy and materia medica RS1-441
spellingShingle	tacrolimus trough concentration variability inflammation Pharmacy and materia medica RS1-441 Anaelle Chavant Xavier Fonrose Elodie Gautier-Veyret Marie Noelle Hilleret Matthieu Roustit Francoise Stanke-Labesque Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?
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 (<i>p</i> = 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), <i>n</i> = 91) than they were for patients with a tacrolimus Cmin ≤ 15 µg/L (13 mg/mL (3–95 mg/L), <i>n</i> = 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.
format	article
author	Anaelle Chavant Xavier Fonrose Elodie Gautier-Veyret Marie Noelle Hilleret Matthieu Roustit Francoise Stanke-Labesque
author_facet	Anaelle Chavant Xavier Fonrose Elodie Gautier-Veyret Marie Noelle Hilleret Matthieu Roustit Francoise Stanke-Labesque
author_sort	Anaelle Chavant
title	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_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_sort	variability of tacrolimus trough concentration in liver transplant patients: which role of inflammation?
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5758fa186e064237851bed4c06b1e063
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Variability of Tacrolimus Trough Concentration in Liver Transplant Patients: Which Role of Inflammation?

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