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Tacrolimus Concentrations Measured in Excreted Bile in Liver Transplant Recipients The STABILE Study

Abstract : Purpose - Tacrolimus (TAC) is the main immunosuppressive drug in liver transplantation. Despite intensive therapeutic drug monitoring (TDM) that relies on whole blood trough concentration (TAC), patients still present with acute cellular rejection or TAC-related toxic effects with concentrations within the therapeutic range. TAC concentration in peripheral blood mononuclear cells (TAC) is considered as an efficient surrogate marker of TAC efficacy. However, it is still not applicable in daily practice. New TDM methods are therefore needed, especially during the early postoperative period. TAC is metabolized in the liver and eliminated through biliary excretion. We therefore hypothesised that TAC concentration measured in excreted bile (TAC) could be a relevant surrogate marker of its efficacy. Methods - The Therapeutic Drug Monitoring of Tacrolimus Biliary Concentrations for Liver-Transplanted Patients (STABILE) study is a prospective monocentric trial. During the 7 first days after TAC therapy initiation, TAC was measured. The correlation between TAC and TAC as well as between TAC and TAC was assessed. The correlations between TAC and liver graft function parameter or with occurrence of neurologic toxic effects were also evaluated. Findings - Between May 2016 and April 2017, 41 patients were analyzed. TAC was significantly correlated with TAC (r = 0.25, P = 0.007). However, a better correlation was found between TAC and TAC (r = 0.53, P < 0.001) and was confirmed in multivariate analysis. However, only TAC was significantly correlated with liver graft function, such as factor V (r = 0.40, P = 0.009) or bilirubin level (r = 0.21, P = 0.01), and significantly lower in patients presenting with neurologic toxic effects (P < 0.001). Receiver operating characteristic curve analysis found that a TAC level lower than 0.20 ng/mL on day 2 after TAC therapy initiation was a good predictive marker of occurrence of neurotoxic effects (AUC = 0.81). Implications - TAC is not a better surrogate maker of TAC activity than TAC. However, TAC could help predict the occurrence of TAC toxic effects when a T-tube is inserted. identifier: NCT02820259.
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Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Wednesday, January 9, 2019 - 4:13:27 PM
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Michel Rayar, Camille Tron, Clara Locher, Alexandre Chebaro, Jean-Marie Beaurepaire, et al.. Tacrolimus Concentrations Measured in Excreted Bile in Liver Transplant Recipients The STABILE Study. Clinical Therapeutics, Elsevier, 2018, 40 (12), pp.2088-2098. ⟨10.1016/j.clinthera.2018.10.015⟩. ⟨hal-01975939⟩



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