Therapeutic Drug Monitoring of Posaconazole: a Monocentric Study with 54 Adults

被引:94
作者
Lebeaux, David
Lanternier, Fanny [1 ]
Elie, Caroline [2 ]
Suarez, Felipe [3 ]
Buzyn, Agnes [3 ]
Viard, Jean-Paul
Bougnoux, Marie-Elisabeth [4 ]
Lecuit, Marc [5 ]
Jullien, Vincent [6 ]
Lortholary, Olivier [7 ]
机构
[1] Univ Paris 05, Hop Necker Enfants Malad, Ctr Infectiol Necker Pasteur, Serv Malad Infect & Trop, F-75743 Paris 15, France
[2] Hop Necker Enfants Malad, Serv Biostat, Paris, France
[3] Hop Necker Enfants Malad, Serv Hematol Clin, Paris, France
[4] Hop Necker Enfants Malad, Microbiol Serv, Paris, France
[5] Inst Pasteur, INSERM, Avenir U604, Grp Microorganismes & Barrieres Hote, F-75724 Paris, France
[6] Hop St Vincent de Paul, INSERM, U663, Serv Pharmacol Clin, F-75674 Paris, France
[7] Inst Pasteur, CNRS, URA 3012, Ctr Natl Reference Mycol & Antifong, Paris, France
关键词
CELL TRANSPLANT RECIPIENTS; VERSUS-HOST-DISEASE; ORAL POSACONAZOLE; EUROPEAN COMMITTEE; HEALTHY-SUBJECTS; PHARMACOKINETICS; SAFETY; VORICONAZOLE; FLUCONAZOLE; EFFICACY;
D O I
10.1128/AAC.00939-09
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Posaconazole is a potent broad-spectrum triazole antifungal. Little is known about the prevalence and risk factors for low plasma posaconazole concentrations (PPCs). We retrospectively reviewed all adult patients whose PPCs were measured after at least 5 days of treatment between April 2006 and July 2008 at the Hopital Necker Enfants Malades. A low PPC was defined as a concentration lower than 500 ng/ml. Fifty-four patients were included: 36 receiving prophylactic (200 mg three times a day) and 18 receiving curative ( 400 mg twice a day) posaconazole therapy. The prevalence of low PPCs was 44% (16/36) in the prophylaxis group and 22% (4/18) in the curative-treatment group. In the prophylaxis group, low PPCs tended to be more frequent in cases of digestive disease (62.5% versus 30%; P = 0.051) and were significantly more frequent among patients with diarrhea (71.4% versus 27%; P = 0.009) or mucositis (100% versus 33%; P = 0.004). In the curative-treatment group, low PPCs were significantly more frequent in cases of diarrhea (75% versus 7%; P = 0.018). In the prophylaxis group, the only two patients who subsequently developed invasive fungal infections exhibited low PPCs. The only adverse event was hepatotoxicity for 2/54 patients (3.7%), which was not related to high plasma drug concentrations. In conclusion, low PPC is common, significantly more frequent in cases of diarrhea or mucositis, and potentially associated with subsequent invasive fungal infection. Therapeutic drug monitoring of posaconazole is therefore mandatory for immunosuppressed adults, at least for those with gastrointestinal disorders.
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收藏
页码:5224 / 5229
页数:6
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