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Master Thesis

Mise au point et validation d’une méthode de dosage de la fraction libre plasmatique de 8 β-lactamines et application chez des patients de réanimation

Abstract : Our work is part of a prospective study called "hyperclairance" with the aim of determining whether augmented renal clearance can lead to a risk of microbiological and clinical failure because of a decrease in free fraction of plasma concentrations for 8 β-lactams (cefepime, ceftazidime, meropenem, ceftriaxone, cefotaxime, cefazoline, piperacillin and tazobactam). In the absence of a method for the simultaneous determination of the free fraction of the antibiotics included in the study, the goal is to develop such a method and then to implement it on plasma samples from the patients in intensive care unit. The development of a method for dosing the free fraction of drugs is somewhat complex compared to the dosage of the total fraction. The protein-drug binding is influenced by certain parameters such as pH, temperature or the composition of the plasma matrix itself. Added to this are other issues such as protein concentration-de! pendent binding, nonspecific binding to devices and the lack of stability of some analytes that may further complicate the development and the dosage of the free fraction. Given the nature of the molecules to be dosed and the difference in composition between plasma blanks and matrix of the target population, the method was validated by loading the calibrators after the ultrafiltration in a filtrate derived from a plasma pool of healthy donors. Thus, the recovery of ultrafiltration was evaluated to determine a correction factor for each drug and intended to be applied to the results of the dosages of the patients. The dosing method, validated according to the recommendations of the European Medicines Agency, will include a first ultrafiltration step followed by a solid phase extraction step and finally a HPLC-UV step for the separation and the quantification.
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Master Thesis
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https://dumas.ccsd.cnrs.fr/dumas-03476914
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Submitted on : Monday, December 13, 2021 - 11:33:29 AM
Last modification on : Tuesday, December 14, 2021 - 3:56:59 AM

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Pharmacie_2019_d_Houdain.pdf
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  • HAL Id : dumas-03476914, version 1

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Nicolas d'Houdain. Mise au point et validation d’une méthode de dosage de la fraction libre plasmatique de 8 β-lactamines et application chez des patients de réanimation. Sciences du Vivant [q-bio]. 2018. ⟨dumas-03476914⟩

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