title: Subtherapeutic Posaconazole Exposure and Treatment Outcome in Patients With Invasive Fungal Disease.
abstract: BACKGROUND
  Posaconazole exposure seems to be subtherapeutic in some patients with invasive fungal disease. Due to the pharmacokinetic variability of posaconazole, therapeutic drug monitoring may help to optimize the efficacy of this antifungal drug.
  
  
  METHODS
  A retrospective study of patients treated with posaconazole from January 2008 to April 2014 and for whom posaconazole serum concentrations were available was conducted. Risk factors for underexposure of posaconazole were detected, and the relationship between posaconazole exposure and treatment outcome according to the European Organization for Research and Treatment of Cancer (EORTC) criteria was assessed.
  
  
  RESULTS
  Seventy patients met the inclusion criteria, 45 patients received posaconazole as treatment, and 25 patients received posaconazole as a prophylactic. Posaconazole serum trough concentrations were <1.25 mg/L in 44.4% of patients receiving treatment and <0.7 mg/L in 40.0% of patients receiving prophylactic posaconazole. Multiple linear regression analysis showed a significant, independent, and negative association of the posaconazole serum trough concentration with a lack of enteral nutrition (P < 0.001), vomiting (P = 0.035), the use of a proton pump inhibitor or H2-receptor antagonist (P < 0.001), a liquid diet (P = 0.002), concomitant chemotherapy (P = 0.004), and a posaconazole dose frequency of 2 times daily (P = 0.015). A higher posaconazole concentration was associated with a better treatment outcome [odds ratio = 22.22 (95% confidence interval, 3.40-145.33); P = 0.001].
  
  
  CONCLUSIONS
  Posaconazole exposure is insufficient in more than 40% of patients at risk of or with invasive fungal disease, and posaconazole exposure is positively correlated with a successful treatment outcome. Therapeutic drug monitoring of posaconazole can detect underexposure and can be helpful in treatment optimization.
authors.affiliation: Departments of *Hematology; †Clinical Pharmacy and Pharmacology; ‡Epidemiology; and §Internal Medicine and Pulmonary Diseases and Tuberculosis, University of Groningen, University Medical Center Groningen, the Netherlands; and ¶Department of Pharmacy, Section Pharmacotherapy and Pharmaceutical Care, University of Groningen, the Netherlands.
authors.forename: Kim C M
authors.initials: KC
authors.lastname: van der Elst
authors.forename: Charlie H S
authors.initials: CH
authors.lastname: Brouwers
authors.forename: Edwin R
authors.initials: ER
authors.lastname: van den Heuvel
authors.forename: Marjolijn J P
authors.initials: MJ
authors.lastname: van Wanrooy
authors.forename: Donald R A
authors.initials: DR
authors.lastname: Uges
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.forename: Lambert F R
authors.initials: LF
authors.lastname: Span
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009181:Mycoses / Q000188:drug therapy* / Q000517:prevention & control; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole