title: Pharmacokinetics of posaconazole prophylaxis of patients with acute myeloid leukemia.
abstract: Antifungal prophylaxis is routinely given to patients with hematologic malignancies at high risk for invasive fungal infections (IFI), yet breakthrough IFI may still occur. Posaconazole emerged as an excellent alternative for fungal prophylaxis in high-risk patients. There is limited data about pharmacokinetics and plasma concentrations of posaconazole when given as prophylaxis in patients with hematologic malignancies. We recruited 20 adult patients for prospective, open label trial of posaconazole given as a prophylaxis in patients with newly diagnosed acute myeloid leukemia (AML) undergoing induction chemotherapy or first salvage therapy. The median age of all patients was 65 years and received prophylaxis for a median of 38 days (range: 5-42 days).Ten patients (50%) completed 42 days on posaconazole prophylaxis. Median plasma posaconazole levels showed no statistical difference across gender, body surface area, patients developing IFI, and patients acquiring grade 3 or 4 elevation of liver enzymes. However, there was an overall trend for higher trough concentrations among patients with no IFI than those with IFI. Pharmacokinetics of posaconazole varies from patient to patient, and AML patients receiving induction chemotherapy who never develop IFI tend to have higher plasma concentrations after oral administration of posaconazole.
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Mattiuzzi
authors.affiliation: Department of Hematology and Oncology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Musa
authors.initials: M
authors.lastname: Yilmaz
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Elias
authors.initials: E
authors.lastname: Jabbour
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Brown
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA. Electronic address: jcortes@mdanderson.org.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005260:Female; D006801:Humans; D060828:Induction Chemotherapy; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D011446:Prospective Studies; D016879:Salvage Therapy; D014230:Triazoles / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
keywords: Acute leukemia; Antifungal prophylaxis; Posaconazole