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Master Thesis

Variabilité des concentrations plasmatiques résiduelles de voriconazole chez le patient allogreffé de cellules souches hématopoïétiques : impact des facteurs génétiques et des comédications

Abstract : Voriconazole (VRC) plasma trough concentrations (VRC Cmin) are highly variable, that could affect treatment efficacy and safety in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). The objectives of this study were to describe the intra- and inter-individual variabilities of VRC Cmin throughout the course of VRC therapy and to identify the determinants of these variabilities of the first and the subsequent VRC Cmin. Clinical data, medications and VRC Cmin (n=308) of 33 AHSCT patients were retrospectively collected. Genotypes of CYP2C19 and CYP3A were determined before allograft. A genetic score combining both CYP2C19 and 3A genotypes was calculated.VRC Cmin inter- and intra-individual coefficients of variation were 84 % and 68 % respectively. VRC dose was correlated to VRC Cmin (r=0.412, p<0.0001) only for oral treatment. Initial VRC Cmin was significantly affected by the route of administration and the genetic score. For oral VRC therapy, patients having a genetic score <2 had higher initial VRC Cmin/D compared to patients with a genetic score >2 (p=0.009). Following VRC Cmin remained influenced by the genetic score (p=0.004), but were also affected by pump proton inhibitor (PPI) comedication (p<0.0001). VRC Cmin displayed a high variability in AHSCT patients partially explained by the route of administration, the treatment with PPI and the genetic score. This study suggests the interest of CYP2C19 and 3A4 genotyping to individualize a priori the first VRC dose, and underlines the need of longitudinal therapeutic drug monitoring to adapt the following doses to maintain VRC Cmin within the therapeutic range.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-01170714
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Submitted on : Thursday, July 2, 2015 - 11:23:27 AM
Last modification on : Wednesday, July 15, 2020 - 8:56:03 AM
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  • HAL Id : dumas-01170714, version 1

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Élodie Gautier-Veyret. Variabilité des concentrations plasmatiques résiduelles de voriconazole chez le patient allogreffé de cellules souches hématopoïétiques : impact des facteurs génétiques et des comédications. Sciences pharmaceutiques. 2014. ⟨dumas-01170714⟩

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