title: Therapeutic drug monitoring of posaconazole: a monocentric study with 54 adults.
abstract: 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 Hôpital 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.
authors.affiliation: Université Paris Descartes, Service des Maladies Infectieuses et Tropicales, Hôpital Necker Enfants Malades, Centre d'Infectiologie Necker-Pasteur, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Lebeaux
authors.forename: Fanny
authors.initials: F
authors.lastname: Lanternier
authors.forename: Caroline
authors.initials: C
authors.lastname: Elie
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.forename: Agnès
authors.initials: A
authors.lastname: Buzyn
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Viard
authors.forename: Marie-Elisabeth
authors.initials: ME
authors.lastname: Bougnoux
authors.forename: Marc
authors.initials: M
authors.lastname: Lecuit
authors.forename: Vincent
authors.initials: V
authors.lastname: Jullien
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003967:Diarrhea / Q000097:blood / Q000188:drug therapy; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000097:blood / Q000188:drug therapy; D009181:Mycoses / Q000188:drug therapy* / Q000517:prevention & control; D012189:Retrospective Studies; D014230:Triazoles / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole