Abstract
This systematic review and meta-analysis examined the optimal trough concentration of voriconazole for adult patients with invasive fungal infections. We used stepwise cutoffs of 0.5–2.0 μg/mL for efficacy and 3.0–6.0 μg/mL for safety. Studies were included if they reported the rates of all-cause mortality and/or treatment success, hepatotoxicity, and nephrotoxicity according to the trough concentration. Twenty-five studies involving 2554 patients were included. The probability of mortality was significantly decreased using a cutoff of ≥1.0 μg/mL (odds ratio (OR) = 0.34, 95% confidence interval (CI) = 0.15–0.80). Cutoffs of 0.5 (OR = 3.48, 95% CI = 1.45–8.34) and 1.0 μg/mL (OR = 3.35, 95% CI = 1.52–7.38) also increased the treatment success rate. Concerning safety, significantly higher risks of hepatotoxicity and neurotoxicity were demonstrated at higher concentrations for all cutoffs, and the highest ORs were recorded at 4.0 μg/mL (OR = 7.39, 95% CI = 3.81–14.36; OR = 5.76, 95% CI 3.14–10.57, respectively). Although further high-quality trials are needed, our findings suggest that the proper trough concentration for increasing clinical success while minimizing toxicity is 1.0–4.0 μg/mL for adult patients receiving voriconazole therapy.
Highlights
IntroductionVoriconazole serum concentrations are highly variable because of its non-linear pharmacokinetics, and they are further influenced by factors such as drug interaction, altered intestinal absorption, and genetic polymorphism
Voriconazole is a triazole with broad-spectrum activity against most clinically significant yeasts and molds [1,2,3], and it is available as both oral and intravenous formulations.Voriconazole serum concentrations are highly variable because of its non-linear pharmacokinetics, and they are further influenced by factors such as drug interaction, altered intestinal absorption, and genetic polymorphism
The present study evaluated the relationship between the reported voriconazole trough concentration and mortality as the primary endpoint, and the secondary aim was to reassess the efficacy and safety of this concentration in adults with IFIs using a systematic review and meta-analysis
Summary
Voriconazole serum concentrations are highly variable because of its non-linear pharmacokinetics, and they are further influenced by factors such as drug interaction, altered intestinal absorption, and genetic polymorphism. These pharmacokinetic variabilities have important implications for dosage adjustment because of unpredictable changes in drug exposure. Therapeutic drug monitoring (TDM) is used to guide voriconazole therapy to prevent drug-related adverse events and improve clinical responses by individualizing dose regimens [4,5]. This guidance was primarily based on a meta-analysis of observational studies by Hamada et al [11]. The revised version includes the results of a pediatric meta-analysis [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
