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Clinical Trial
. 2012 Dec;56(12):6298-303.
doi: 10.1128/AAC.01177-12. Epub 2012 Oct 1.

Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplastic syndrome

Affiliations
Clinical Trial

Therapeutic drug monitoring of posaconazole in patients with acute myeloid leukemia or myelodysplastic syndrome

M Vaes et al. Antimicrob Agents Chemother. 2012 Dec.

Abstract

Posaconazole is a broad-spectrum triazole antifungal available as an oral suspension. Pharmacokinetic data showed a high variability of plasma posaconazole concentrations (PPCs) in patients, suggesting a potential interest in drug monitoring. The aim of our prospective study was to measure the PPCs in prophylactically treated patients to evaluate the impact of different factors on these concentrations. In 40 patients treated prophylactically with posaconazole for acute myeloid leukemia or myelodysplastic syndrome between February 2009 and August 2010, PPCs were measured at day 7 of treatment and then twice weekly. Demographic data, clinical data (including gastrointestinal disorders, comedications, and treatment compliance), caloric and fat intake, and biological data were collected and evaluated. We obtained 275 measurements of PPCs, with a median of 430 ng/ml. PPCs were significantly lower in patients with mucositis (P < 0.001), nausea (P = 0.03), diarrhea (P = 0.03), or vomiting (P = 0.05). PPCs were higher in patients with a higher caloric intake (P = 0.02), while the proportion of fat intake had no influence on PPCs (P = 0.84). The concomitant use of proton pump inhibitors decreased the PPCs (P = 0.02), while the use of tacrolimus increased the PPC (P = 0.03). In the multivariate analysis, the factors influencing the PPCs independently were the concomitant use of tacrolimus (P < 0.001), the presence of mucositis (P = 0.01), and food intake (P = 0.02). Our study confirmed the high variability of posaconazole bioavailability and showed the significant influence of gastrointestinal disorders, food intake, and concomitant medication on the PPCs. However, the optimal PPCs still remain to be defined and correlated with clinical efficacy.

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Figures

Fig 1
Fig 1
Distribution of plasma posaconazole concentrations at T0.
Fig 2
Fig 2
Intraindividual coefficients of variation in patients with at least 5 plasma posaconazole concentration measurements.

References

    1. Alffenaar J-WC, van Assen S, van der Werf TS, Kosterink JGW, Uges DRA. 2009. Omeprazole significantly reduces posaconazole serum trough level. Clin. Infect. Dis. 48:839. - PubMed
    1. Andes D, Pascual A, Marchetti O. 2009. Antifungal therapeutic drug monitoring: established and emerging indications. Antimicrob. Agents Chemother. 53:24–34 - PMC - PubMed
    1. Conte JE, Jr, et al. 2009. Intrapulmonary pharmacokinetics and pharmacodynamics of posaconazole at steady state in healthy subjects. Antimicrob. Agents Chemother. 53:703–707 - PMC - PubMed
    1. Cornely OA, et al. 2007. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N. Engl. J. Med. 356:348–359 - PubMed
    1. Courtney R, Pai S, Laughlin M, Lim J, Batra V. 2003. Pharmacokinetics, safety, and tolerability of oral posaconazole administered in single and multiple doses in healthy adults. Antimicrob. Agents Chemother. 47:2788–2795 - PMC - PubMed

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