%0 Journal Article
%T Effectiveness and safety of the simulation-based first-dose design of voriconazole.
%A Umemura T
%A Kakizaki H
%A Mutoh Y
%A Mizuno T
%A Ito Y
%A Hioki T
%A Kato H
%A Hagihara M
%A Yamada T
%A Ikeda Y
%A Mikamo H
%A Ichihara T
%A Hamada Y
%J J Infect Chemother
%V 0
%N 0
%D 2024 Jun 27
%M 38944383
%F 2.065
%R 10.1016/j.jiac.2024.06.016
%X <B>BACKGROUND: </B>We investigated whether the initial voriconazole (VRCZ) dosing design, as determined using simulation software with a population pharmacokinetic model of Japanese patients, impacts the effectiveness and safety when compared with VRCZ initiation according to the package insert.<BR><B>METHODS: </B>In this single-center retrospective observational study, we employed records from Tosei General Hospital (a 633-bed hospital), dated April 2017 to September 2023. Eligible patients were divided into the software-based simulation group, comprising patients administered initial VRCZ dosage adjustment by pharmacists using software-based simulation, and the standard therapy group, whose dosage was administered by a physician following the package insert recommendations without simulation. The primary objective of this study was to determine the efficacy of VRCZ first-dose design in reducing the incidence of hepatotoxicity and visual symptoms.<BR><B>RESULTS: </B>The median ages of enrolled participants (n = 93) were 75 (68-79) and 72 (65-78) years in the software-based simulation and standard therapy groups, respectively. Regardless of formulation, initial trough concentrations were lower in the VRCZ software-based first dosage adjustment group and higher rate within the appropriate range (1-4 μg/mL). The incidence of all-grade hepatotoxicity or visual symptoms was significantly lower in the software-based simulation group. The log-rank test revealed a significant impact on the occurrence of ≥grade 2 hepatotoxicity in the software-based first dosage adjustment group compared to that in the standard therapy group.<BR><B>CONCLUSIONS: </B>The initial VRCZ dosing design using simulation software improved the achievement of appropriate initial trough concentrations and resulted in fewer occurrences of hepatotoxicity (≥grade 2) when compared with the standard therapy.