title: Pharmacodynamic studies of voriconazole: informing the clinical management of invasive fungal infections.
abstract: Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections (IFI), including aspergillosis, candidiasis, Scedosporium infection, and Fusarium infection. IFI often occur in immunocompromised patients, leading to increased morbidity and mortality.
  
  
  
  The objective of this review is to summarize the pharmacodynamic properties of voriconazole and to provide considerations for potential optimal dosing strategies. Studies have demonstrated superior clinical response when an AUC/MIC >25 or Cmin/MIC >1 is attained in adult patients, correlating to a trough concentration range as narrow as 2-4.5 mg/L; however, these targets are poorly established in the pediatric population. Topics in this discussion include voriconazole use in multiple age groups, predisposing patient factors for IFI, and considerations for clinicians managing IFI. Expert commentary: The relationship between voriconazole dosing and exposure is not well defined due to the large inter- and intra-subject variability. Development of comprehensive decision support tools for individualizing dosing, particularly in children who require higher dosing, will help to increase the probability of achieving therapeutic efficacy and decrease sub-therapeutic dosing and adverse events.
authors.affiliation: a Division of Clinical Pharmacology , University of Utah , Salt Lake City , UT , USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Job
authors.affiliation: b Pharmacy, Primary Children's Hospital, Intermountain Healthcare , University of Utah , Salt Lake City , UT , USA.
authors.forename: Jared
authors.initials: J
authors.lastname: Olson
authors.affiliation: c Division of Pediatric Infectious Diseases, Department of Pediatrics , University of Utah , Salt Lake City , UT , USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Stockmann
authors.affiliation: a Division of Clinical Pharmacology , University of Utah , Salt Lake City , UT , USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Constance
authors.affiliation: a Division of Clinical Pharmacology , University of Utah , Salt Lake City , UT , USA.|d Division of Microbiology and Immunology, Department of Pathology , University of Utah , Salt Lake City , UT , USA.
authors.forename: Elena Y
authors.initials: EY
authors.lastname: Enioutina
authors.affiliation: a Division of Clinical Pharmacology , University of Utah , Salt Lake City , UT , USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Rower
authors.affiliation: a Division of Clinical Pharmacology , University of Utah , Salt Lake City , UT , USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Linakis
authors.affiliation: a Division of Clinical Pharmacology , University of Utah , Salt Lake City , UT , USA.
authors.forename: Alfred H
authors.initials: AH
authors.lastname: Balch
authors.affiliation: a Division of Clinical Pharmacology , University of Utah , Salt Lake City , UT , USA.
authors.forename: Tian
authors.initials: T
authors.lastname: Yu
authors.affiliation: a Division of Clinical Pharmacology , University of Utah , Salt Lake City , UT , USA.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Liu
authors.affiliation: c Division of Pediatric Infectious Diseases, Department of Pediatrics , University of Utah , Salt Lake City , UT , USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Thorell
authors.affiliation: a Division of Clinical Pharmacology , University of Utah , Salt Lake City , UT , USA.|e Department of Pharmacology and Toxicology, College of Pharmacy , University of Utah , Salt Lake City , UT , USA.
authors.forename: Catherine M T
authors.initials: CM
authors.lastname: Sherwin
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease; D006801:Humans; D000072742:Invasive Fungal Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D065819:Voriconazole / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole
keywords: Aspergillus; CYP2C19; Candida; Voriconazole; anti-fungal agent; invasive fungal infection; neonates; pediatrics; pharmacodynamics; therapeutic drug monitoring