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Master Thesis

Développement et validation d’une méthode de dosage de l’Entécavir : application pour l’étude de l’observance au traitement chez des patients chroniquement infectés par le virus de l’hépatite B

Abstract : Entecavir is a nucleoside analog, available for the treatment of chronic hepatitis B. We report here a method suitable for the quantitation of entecavir in plasma of chronically infected HBV patients. This method couples a Solid-Phase Extraction (SPE) preparation and a high performance liquid chromatography-tandem mass spectrometry. We used Hydrophilic Interaction Liquid Chromatography (HILIC) columns to improve retention. Our results show good accuracy and precision, for within-day (bias between 3.83 and 7.45 %, CV between 0.67 and 3.83 % respectively) and for between-day (bias between 4.57 and 5.79 %, CV between 3.06 and 6.41 % respectively). The lower and upper limit of quantification were 50 and 10 000 ng. Calibration was found linear over the concentration range of 50.0 to 10 000 ng.L-1 and there was no inter-sample carryover . So performance of this method is in accordance with international guidelines and is compatible with daily laboratory practice and clinical trials. On 80 plasma samples from patients treated with entecavir, only 6 were non-adherent patients. A trend (p = 0.06) to the decrease in median trough concentrations was observed with non-adherent patients (391 ng / L) compared to adherent patients (580 ng / L). No patient had plasma concentration of Entecavir undetectable. In view of the long half-life of Entecavir (about 24 hours), these results suggest that some patients identified by our criteria as "non-observant" are so only occasionally. This work also enabled the description of the pharmacokinetic profile of entecavir in patients with hepatitis B and treated chronically, and the determination of a maximum concentration (Cmax) of 3182 ng / L.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-01254609
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Submitted on : Tuesday, January 12, 2016 - 2:49:19 PM
Last modification on : Tuesday, May 11, 2021 - 11:36:18 AM
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  • HAL Id : dumas-01254609, version 1

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Guillaume Chovelon. Développement et validation d’une méthode de dosage de l’Entécavir : application pour l’étude de l’observance au traitement chez des patients chroniquement infectés par le virus de l’hépatite B. Sciences pharmaceutiques. 2015. ⟨dumas-01254609⟩

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