title: Inflammation is associated with voriconazole trough concentrations.
abstract: Voriconazole concentrations display a large variability, which cannot completely be explained by known factors. Inflammation may be a contributing factor, as inflammatory stimuli can change the activities and expression levels of cytochrome P450 isoenzymes. We explored the correlation between inflammation, reflected by C-reactive protein (CRP) concentrations, and voriconazole trough concentrations. A retrospective chart review of patients with at least one steady-state voriconazole trough concentration and a CRP concentration measured on the same day was performed. A total of 128 patients were included. A significantly (P < 0.001) higher voriconazole trough concentration was observed in patients with severe inflammation (6.2 mg/liter; interquartile range [IQR], 3.4 to 8.7 mg/liter; n = 20) than in patients with moderate inflammation (3.4 mg/liter; IQR, 1.6 to 5.4 mg/liter; n = 60) and in patients with no to mild inflammation (1.6 mg/liter; IQR, 0.8 to 3.0 mg/liter; n = 48). The patients in all three groups received similar voriconazole doses based on mg/kg body weight (P = 0.368). Linear regression analyses, both unadjusted and adjusted for covariates of gender, age, dose, route of administration, liver enzymes, and interacting coadministered medications, showed a significant association between voriconazole and CRP concentration (P < 0.001). For every 1-mg/liter increase in the CRP concentration, the voriconazole trough concentration increased by 0.015 mg/liter (unadjusted 95% confidence interval [CI], 0.011 to 0.020 mg/liter; adjusted 95% CI, 0.011 to 0.019 mg/liter). Inflammation, reflected by the C-reactive protein concentration, is associated with voriconazole trough concentrations. Further research is necessary to assess if taking the inflammatory status of a patient into account is helpful in therapeutic drug monitoring of voriconazole to maintain concentrations in the therapeutic window, thereby possibly preventing suboptimal treatment or adverse events.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: Marjolijn J P
authors.initials: MJ
authors.lastname: van Wanrooy
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Hematology, Groningen, The Netherlands.
authors.forename: Lambert F R
authors.initials: LF
authors.lastname: Span
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Critical Care, Groningen, The Netherlands.
authors.forename: Michael G G
authors.initials: MG
authors.lastname: Rodgers
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: van den Heuvel
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.
authors.forename: Donald R A
authors.initials: DR
authors.lastname: Uges
authors.affiliation: University of Groningen, University Medical Center Groningen, Departments of Internal Medicine and Pulmonary Diseases & Tuberculosis, Groningen, The Netherlands.
authors.forename: Tjip S
authors.initials: TS
authors.lastname: van der Werf
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands University of Groningen, Department of Pharmacy, Division of Pharmacotherapy and Pharmaceutical Care, Groningen, The Netherlands.
authors.forename: Jos G W
authors.initials: JG
authors.lastname: Kosterink
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands j.w.c.alffenaar@umcg.nl.
authors.forename: Jan-Willem C
authors.initials: JW
authors.lastname: Alffenaar
mesh_terms: D000328:Adult; D000367:Age Factors; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D001228:Aspergillosis / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000254:growth & development; D002097:C-Reactive Protein / Q000378:metabolism*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012737:Sex Factors; D065819:Voriconazole / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D002097:C-Reactive Protein; D065819:Voriconazole