title: Posaconazole therapeutic drug monitoring in the real-life setting: a single-center experience and review of the literature.
abstract: OBJECTIVE
  To evaluate the incidence of posaconazole serum levels below 700 μg/L, the rate of breakthrough infections during posaconazole prophylaxis, and factors influencing posaconazole exposure in daily clinical practice.
  
  
  METHODS
  Prospective observational study and review of the literature.
  
  
  METHODS
  Hematology and oncology department in a tertiary care academic medical center.
  
  
  METHODS
  A total of 31 patients with hematologic diseases: 27 received posaconazole prophylaxis and 4 received posaconazole therapy.
  
  
  RESULTS
  We analyzed 187 posaconazole serum levels from 31 patients (median of five posaconazole levels per patient; range 1-16). The analyses revealed that 80 of 187 levels (43%) were below 700 μg/L, and 68% of patients were found to have at least one measured level below this threshold. Breakthrough invasive fungal infections categorized as probable or possible infections occurred in 4 of 27 patients (15%) receiving the drug as prophylaxis. A multivariate analysis, accounting for repeated measurements per patient, revealed that age (p=0.02) and mucositis (p=0.04) were associated with significantly reduced posaconazole serum levels. A review of the current literature on posaconazole therapeutic drug monitoring data from real-world studies is presented as an overview table, highlighting the frequency of patients with inadequate posaconazole exposure and heterogeneity of factors influencing posaconazole levels.
  
  
  CONCLUSIONS
  Therapeutic drug monitoring of posaconazole is an important tool of therapy optimization because oral posaconazole suspension shows unreliable absorption rates and exposure.
authors.affiliation: Department of Hematology & Oncology, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Barbara N
authors.initials: BN
authors.lastname: Gross
authors.forename: Gabriele
authors.initials: G
authors.lastname: Ihorst
authors.forename: Manfred
authors.initials: M
authors.lastname: Jung
authors.forename: Ralph
authors.initials: R
authors.lastname: Wäsch
authors.forename: Monika
authors.initials: M
authors.lastname: Engelhardt
mesh_terms: D000046:Academic Medical Centers; D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006402:Hematologic Diseases / Q000150:complications / Q000188:drug therapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009181:Mycoses / Q000453:epidemiology / Q000517:prevention & control*; D011446:Prospective Studies; D012307:Risk Factors; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole
keywords: antifungal prophylaxis; antifungals; posaconazole; therapeutic drug monitoring