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Therapeutic drug monitoring of posaconazole in hematology adults under posaconazole prophylaxis: influence of food intake

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Abstract

Posaconazole (PCZ) is given at 200 mg three times daily as a fungal prophylaxis in neutropenic hematologic malignancy patients. A relationship between exposure, plasma concentration, and efficacy is suggested. The objectives of this prospective study were to analyze the PCZ plasma concentration in hematology adults at high risk of developing invasive fungal infections (IFIs), and factors that could have an impact on the PCZ plasma concentration. PCZ plasma concentrations were measured after 2, 7, 10, 14, and 21 days of PCZ prophylaxis. Factors such as gender, age, body weight, posology, treatment duration, mucositis, proton pump inhibitor (PPI) use, and food intake were studied. Sixty-three patients were included, with a median age of 52 years (range 17–70) and a median weight of 75 kg (range 47–150). The median PCZ plasma concentration of the 63 patients ranged from 0.42 to 0.48 mg/L. At day 2, 30% of PCZ plasma concentration were under 0.35 mg/L, and at day 7, 74% were <0.70 mg/L. PCZ plasma concentrations were not affected by gender, age, body weight, or treatment duration. We found that food intake had a high influence on PCZ plasma concentrations (p = 0.0049). PCZ was well tolerated. One patient has developed a probable IFI, probably related to a low exposure to PCZ. PCZ therapeutic drug monitoring (TDM) is essential in order to early detect patients with low concentrations, to assess the etiology of such results, and to decide on the treatment strategy to apply.

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Funding

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Authors and Affiliations

  1. Department of Medical Pharmacology and Toxicology, University Hospital of Montpellier, Montpellier, France

    C. Eiden, H. Peyrière, M. Cociglio & D. Hillaire-Buys

  2. Department of Clinical Hematology, University Hospital of Montpellier, Montpellier, France

    J. C. Meniane, P. Ceballos & N. Fegueux

  3. UMR 145, Institut de Recherche pour le Développement, University of Montpellier, Montpellier, France

    H. Peyrière, S. Eymard-Duvernay & J. Reynes

  4. Department of Clinical Pharmacy, University of Montpellier, Montpellier, France

    H. Peyrière

  5. Department of Infectious Diseases, University Hospital of Montpellier, Montpellier, France

    G. Le Falher & J. Reynes

  6. Service de Pharmacologie Médicale et Toxicologie, Hôpital Lapeyronie, 371 Avenue du Doyen Gaston Giraud, 34295, Montpellier Cedex 5, France

    C. Eiden

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  1. C. Eiden
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  2. J. C. Meniane
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  3. H. Peyrière
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  4. S. Eymard-Duvernay
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  5. G. Le Falher
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  7. N. Fegueux
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  8. M. Cociglio
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  9. J. Reynes
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  10. D. Hillaire-Buys
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Corresponding author

Correspondence to C. Eiden.

Additional information

This work was presented in part at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), San Francisco, CA, USA, 12–15 September 2009.

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Eiden, C., Meniane, J.C., Peyrière, H. et al. Therapeutic drug monitoring of posaconazole in hematology adults under posaconazole prophylaxis: influence of food intake. Eur J Clin Microbiol Infect Dis 31, 161–167 (2012). https://doi.org/10.1007/s10096-011-1288-9

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  • DOI: https://doi.org/10.1007/s10096-011-1288-9

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