AUTHOR=Cheng Lin , Liang Zaiming , Liu Fang , Lin Ling , Zhang Jiao , Xie Linli , Yu Mingjie , Sun Fengjun 

TITLE=Factors influencing plasma concentration of voriconazole and voriconazole- N-oxide in younger adult and elderly patients

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1126580

DOI=10.3389/fphar.2023.1126580

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> Voriconazole (VCZ) metabolism is influenced by many factors. Identifying independent influencing factors helps optimize VCZ dosing regimens and maintain its trough concentration (C<sub>0</sub>) in the therapeutic window.</p><p><bold>Methods:</bold> We conducted a prospective study investigating independent factors influencing VCZ C<sub>0</sub> and the VCZ C<sub>0</sub> to VCZ N-oxide concentration ratio (C<sub>0</sub>/C<sub>N</sub>) in younger adults and elderly patients. A stepwise multivariate linear regression model, including the IL-6 inflammatory marker, was used. The receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive effect of the indicator.</p><p><bold>Results:</bold> A total of 463 VCZ C<sub>0</sub> were analyzed from 304 patients. In younger adult patients, the independent factors that influenced VCZ C<sub>0</sub> were the levels of total bile acid (TBA) and glutamic-pyruvic transaminase (ALT) and the use of proton-pump inhibitors. The independent factors influencing VCZ C<sub>0</sub>/C<sub>N</sub> were IL-6, age, direct bilirubin, and TBA. The TBA level was positively associated with VCZ C<sub>0</sub> (<italic>ρ</italic> = 0.176, <italic>p</italic> = 0.019). VCZ C<sub>0</sub> increased significantly when the TBA levels were higher than 10 μmol/L (<italic>p</italic> = 0.027). ROC curve analysis indicated that when the TBA level ≥4.05 μmol/L, the incidence of a VCZ C<sub>0</sub> greater than 5 μg/ml (95% CI = 0.54–0.74) (<italic>p</italic> = 0.007) increased. In elderly patients, the influencing factors of VCZ C<sub>0</sub> were DBIL, albumin, and estimated glomerular filtration rate (eGFR). The independent factors that affected VCZ C<sub>0</sub>/C<sub>N</sub> were eGFR, ALT, γ-glutamyl transferase, TBA, and platelet count. TBA levels showed a positive association with VCZ C<sub>0</sub> (<italic>ρ</italic> = 0.204, <italic>p</italic> = 0.006) and C<sub>0</sub>/C<sub>N</sub> (<italic>ρ</italic> = 0.342, <italic>p</italic> &lt; 0.001). VCZ C<sub>0</sub>/C<sub>N</sub> increased significantly when TBA levels were greater than 10 μmol/L (<italic>p</italic> = 0.025). ROC curve analysis indicated that when the TBA level ≥14.55 μmol/L, the incidence of a VCZ C<sub>0</sub> greater than 5 μg/ml (95% CI = 0.52–0.71) (<italic>p</italic> = 0.048) increased.</p><p><bold>Conclusion:</bold> TBA level may serve as a novel marker for VCZ metabolism. eGFR and platelet count should also be considered when using VCZ, especially in elderly patients.</p>