AUTHOR=Zhou Lijuan , Li Min , Li Huihong , Guo Zhiqiang , Gao Yanqiu , Zhang Hua , Qin Fuli , Sang Zhihui , Xing Qinghe , Cheng Long , Cao Wei 

TITLE=Establishment of a mathematical prediction model for voriconazole stable maintenance dose: a prospective study

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1157944

DOI=10.3389/fcimb.2023.1157944

ISSN=2235-2988

ABSTRACT=<sec><title>Background</title><p>In patients with invasive fungal infection (IFI), the steady-state serum trough concentration (<italic>C</italic><sub>min</sub>) of voriconazole (VCZ) is highly variable and can lead to treatment failure (<italic>C</italic><sub>min</sub> &lt; 0.5 mg/L) and toxicity (<italic>C</italic><sub>min</sub> ≥ 5.0 mg/L). However, It remains challenging to determine the ideal maintenance dose to achieve the desired <italic>C</italic><sub>min</sub> level quickly.</p></sec><sec><title>Aims</title><p>This randomized, prospective observational single-center study aimed to identify factors affecting VCZ-<italic>C</italic><sub>min</sub> and maintenance dose and create an algorithmic model to predict the necessary maintenance dose. MeThe study enrolled 306 adult IFI patients, split into two groups: non-gene-directed (A) (where CYP2C19 phenotype is not involved in determining VCZ dose) and gene-directed (B) (where CYP2C19 phenotype is involved in determining VCZ dose).</p></sec><sec><title>Results</title><p>Results indicated that CYP2C19 genetic polymorphisms might significantly impact VCZ loading and maintenance dose selection. CYP2C19 phenotype, C-reaction protein (CRP), and average daily dose/body weight were significant influencers on VCZ-<italic>C</italic><sub>min</sub>, while CYP2C19 phenotype, CRP, and body weight significantly impacted VCZ maintenance dose. A feasible predictive formula for VCZ stable maintenance dose was derived from the regression equation as a maintenance dose (mg) =282.774-0.735×age (year)+2.946×body weight(Kg)-19.402×CYP2C19 phenotype (UM/RM/NM:0, IM:1, PM:2)-0.316×CRP (mg/L) (<italic>p</italic> &lt; 0.001).</p></sec><sec><title>Discussion</title><p>DiThis formula may serve as a valuable supplement to the Clinical Pharmacogenetics Implementation Consortium (CPIC<sup>®</sup>) guideline for CYP2C19 and VCZ therapy, especially for IFI patients with highly variable inflammatory cytokines during VCZ therapy.</p></sec>