title: Trough concentration of voriconazole and its relationship with efficacy and safety: a systematic review and meta-analysis.
abstract: The optimum trough concentration of voriconazole for clinical response and safety is controversial. The objective of this review was to determine the optimum trough concentration of voriconazole and evaluate its relationship with efficacy and safety.
  
  
  
  MEDLINE, EMBASE, ClinicalTrials.gov, the Cochrane Library and three Chinese literature databases were searched. Observational studies that compared clinical outcomes below and above the trough concentration cut-off value were included. We set the trough concentration cut-off value for efficacy as 0.5, 1.0, 1.5, 2.0 and 3.0 mg/L and for safety as 3.0, 4.0, 5.0, 5.5 and 6.0 mg/L. The efficacy outcomes were invasive fungal infection-related mortality, all-cause mortality, rate of successful treatment and rate of prophylaxis failure. The safety outcomes included incidents of hepatotoxicity, neurotoxicity and visual disorders.
  
  
  
  A total of 21 studies involving 1158 patients were included. Compared with voriconazole trough concentrations of >0.5 mg/L, levels of <0.5 mg/L significantly decreased the rate of treatment success (risk ratio = 0.46, 95% CI 0.29-0.74). The incidence of hepatotoxicity was significantly increased with trough concentrations >3.0, >4.0, >5.5 and >6.0 mg/L. The incidence of neurotoxicity was significantly increased with trough concentrations >4.0 and >5.5 mg/L.
  
  
  
  A voriconazole level of 0.5 mg/L should be considered the lower threshold associated with efficacy. A trough concentration >3.0 mg/L is associated with increased hepatotoxicity, particularly for the Asian population, and >4.0 mg/L is associated with increased neurotoxicity.
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China Department of Pharmacy, The Affiliated Hospital of Medical College, Ningbo University, Ningbo, Zhejiang, China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Jin
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China Department of Pharmacy Administration and Clinical Pharmacy, Peking University School of Pharmaceutical Sciences, Beijing, China tiansheng_wang@yahoo.com.
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Pharmacy and Therapeutics, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Falcione
authors.affiliation: Department of Pharmacy Practice, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Olsen
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China Department of Pharmacy Administration and Clinical Pharmacy, Peking University School of Pharmaceutical Sciences, Beijing, China.
authors.forename: Ken
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Pharmacy, Stanford University Hospital and Clinics, Palo Alto, CA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Hui
authors.affiliation: Department of Pharmacy, Peking University Third Hospital, Beijing, China.
authors.forename: Suodi
authors.initials: S
authors.lastname: Zhai
mesh_terms: D000935:Antifungal Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D016903:Drug Monitoring; D006801:Humans; D000072742:Invasive Fungal Infections / Q000188:drug therapy* / Q000517:prevention & control; D008099:Liver / Q000187:drug effects; D009181:Mycoses / Q000188:drug therapy* / Q000517:prevention & control; D009420:Nervous System / Q000187:drug effects; D016896:Treatment Outcome; D065819:Voriconazole / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*
chemical_list: D000935:Antifungal Agents; D065819:Voriconazole