Is there an interest of new techniques for dosing posaconazole in invasive fungal infection prophylaxis?
Résumé
: Invasive fungal infections (IFI) are a major cause
of morbidity and mortality in patients treated for acute
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myeloid leukemia (AML) or those receiving allogeneic stem
cell transplant (SCT). The interest of IFI prophylaxis by
posaconazole (PCZ), an anti-fungal molecule with intramembrane mechanism of action, in these settings is well
proved. Despite the threshold of 0.7 mg/l considered to the
goal in prophylaxis indication, usefulness of therapeutic drug
monitoring (TDM) of PCZ is still questionable because both
poor plasma levels reached in practice and the absence of
demonstrated correlation between blood and membrane
levels. We evaluate the interest of the dosage of different
sub-fractions of posaconazole and correlate them with
confusion parameters known to influence results of PCZ
monitoring.
Material (or patients) and methods: Samples from the TDM of
PCZ (oral suspension) performed in hematological malignancies
between January and April 2015 in our laboratory were
prospectively collected. In more, we measured the total fraction
(TF) after hydrolysis of the glucuroconjugate, and the fraction in
erythrocyte membrane (EF) of PCZ. We calculated the
conjugated fraction (GF = TF - UF) and the ratio of conjugation.
Results were correlated with 13 confusion parameters: indication of prophylaxis, body-mass index and surface area, ethnicity,
fever, nutrition mode, hemoglobin concentration, white blood
cell count, glomerular filtration rate (GFR), albumin, intake of
proton pump inhibitors, immunosuppressive drugs (IS), and
corticosteroids.