title: Pharmacokinetic and Pharmacodynamic Properties of Oral Voriconazole in Patients with Invasive Fungal Infections.
abstract: OBJECTIVE
  To assess the pharmacokinetic and pharmacodynamic (PK/PD) properties of voriconazole and to investigate the relationship between PK/PD parameters and the efficacy of a fixed-dose oral regimen in the treatment of invasive fungal infections (IFIs).
  
  
  METHODS
  Prospective and observational PK/PD study.
  
  
  METHODS
  A university-affiliated medical center.
  
  
  METHODS
  Fifteen hospitalized patients with proven IFIs who were treated with oral voriconazole for at least 2 weeks.
  
  
  METHODS
  We investigated the PK/PD properties of voriconazole using a noncompartmental analysis in 15 patients.
  
  
  RESULTS
  Marked interpatient variation in voriconazole pharmacokinetic properties was noted including peak plasma concentrations (median 2.31 mg/L, range 1.06-4.01 mg/L), 12-hour area under the plasma concentration-time curve (AUCτ ) (median 21.18 hr mg/L, range 7.71-42.07 hr mg/L), ratio of the unbound drug AUC over 24 hours (fAUC24 ) divided by the minimum inhibitory concentration (fAUC24 :MIC; median 62.61, range 6.48-415.30), and the free trough plasma concentration (Cmin ) divided by the MIC (fCmin :MIC; median 1.81, range 0.46-15.52). There was a good correlation between voriconazole Cmin and AUCτ (R(2)  = 0.805). Voriconazole therapy was effective in 66.7% of patients (10/15). No significant difference was observed with regard to successful clinical response between the patients with a fAUC24 :MIC and fCmin :MIC values higher than 25 and higher than 1 (10/12 vs 10/13, respectively; χ(2)  = 1.61, p=0.688).
  
  
  CONCLUSIONS
  There is substantial interpatient variability in the PK/PD properties of voriconazole. fAUC24 :MIC values higher than 25 and fCmin :MIC values higher than 1 may predict clinical response in patients with IFIs. Designing an optimal dosage regimen based on individual PK/PD properties will improve the efficacy in patients with IFIs.
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Taotao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jin'e
authors.initials: J
authors.lastname: Lei
authors.affiliation: Central Intensive Care Unit, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Qianting
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Limei
authors.initials: L
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000046:Academic Medical Centers; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D019540:Area Under Curve; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008954:Models, Biological; D009181:Mycoses / Q000188:drug therapy*; D011446:Prospective Studies; D065819:Voriconazole / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole
keywords: fAUC24:MIC; fCmin:MIC; invasive fungal infections; noncompartmental analysis; pharmacodynamics; pharmacokinetics; voriconazole