Analysis of Factors Affecting Variability in Dose-Normalized Voriconazole Trough Concentrations: A Single-Center Retrospective Study

LIU Yanling; QIN Wenjie; YANG Zhiling; DENG Yinhua

PDF(2013 KB)

Journal of Hunan Normal University(Medical Science) ›› 2026, Vol. 23 ›› Issue (3) : 133-137.

Analysis of Factors Affecting Variability in Dose-Normalized Voriconazole Trough Concentrations: A Single-Center Retrospective Study

LIU Yanling, QIN Wenjie, YANG Zhiling, DENG Yinhua

Author information +

History +

Abstract

Objective To investigate the distribution characteristics of voriconazole trough concentrations and the factors influencing their variability, and to provide a basis for individualized therapy. Methods A retrospective study was conducted in patients receiving voriconazole therapy with therapeutic drug monitoring. Clinical data were collected and voriconazole plasma concentrations were determined using high-performance liquid chromatography. Differences in trough concentrations across clinical characteristics and concomitant medications were analyzed. The dose-normalized trough concentration (Cmin/Dose) was calculated as the trough concentration divided by the corresponding daily dose. Univariate and multivariate linear regression analyses were performed to identify independent factors affecting drug exposure. Results A total of 267 patients were included. The daily dose of voriconazole ranged from 50 to 640 mg. Among them, 11.6% of patients had trough concentrations below the effective lower limit (<1.0 μg/mL), and 13.48% exceeded the safety upper limit (>5.5 μg/mL). Trough concentrations were significantly associated with age and loading dose. Multivariate analysis identified total bilirubin as an independent factor influencing dose-normalized trough concentrations (P<0.001). Conclusion Voriconazole trough concentrations exhibit substantial interindividual variability. Total bilirubin may serve as an important predictor of concentration changes and has clinical value for individualized dosing under therapeutic drug monitoring.

Key words

voriconazole / plasma concentration / drug monitoring / dose-normalization / individualized therapy

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

LIU Yanling, QIN Wenjie, YANG Zhiling, DENG Yinhua. Analysis of Factors Affecting Variability in Dose-Normalized Voriconazole Trough Concentrations: A Single-Center Retrospective Study[J]. Journal of Hunan Normal University(Medical Science). 2026, 23(3): 133-137

References

[1] WANG J, SUN J, YANG DW, et al.Appraisal of guidelines and variations in recommendations on drug therapy for invasive aspergillosis prevention and treatment[J]. Front Pharmacol, 2025, 16: 1443487.
[2] HUBRECHTS J, GIJSEN M, FLORE K, et al.Unravelling voriconazole's hepatic metabolism: a narrative review on factors impacting voriconazole-N-oxide exposure[J]. Mycoses, 2026, 69(2): e70158.
[3] SALEH A, SCHULZ J, SCHLENDER JF, et al.Understanding voriconazole metabolism: a middle-out physiologically-based pharmacokinetic modelling framework integrating in vitro and clinical insights[J]. Clin Pharmacokinet, 2024, 63(11): 1609-1630.
[4] TAKESUE Y, HANAI Y, ODA K, et al.Clinical practice guideline for the therapeutic drug monitoring of voriconazole in non-Asian and Asian adult patients: consensus review by the Japanese society of chemotherapy and the Japanese society of therapeutic drug monitoring[J]. Clin Ther, 2022, 44(12): 1604-1623.
[5] 陈丽娟, 朱蕻潮, 吴晓丽, 等. 伏立康唑血药浓度监测在患者肝毒性和视觉症状不良反应预测诊断中的应用价值[J]. 中国新药与临床杂志, 2025, 44(2): 139-144.
[6] ASAI Y, KATO H, TAWARA I, et al.Potential of albumin-bilirubin score for estimating the voriconazole-induced hepatotoxicity undergoing therapeutic drug monitoring: a single-center retrospective cohort study[J]. Clin Ther, 2025, 47(4): 330-334.
[7] ZHAO YC, ZOU Y, HOU JJ, et al.Factors affecting voriconazole trough concentration and optimal maintenance voriconazole dose in Chinese children[J]. Antibiotics (Basel), 2021, 10(12): 1542.
[8] ZUBIAUR P, KNELLER LA, OCHOA D, et al.Evaluation of voriconazole CYP2C19 phenotype-guided dose adjustments by physiologically based pharmacokinetic modeling[J]. Clin Pharmacokinet, 2021, 60(2): 261-270.
[9] 赖芳圆, 朱理想, 刘婷, 等. 血液肿瘤科儿童伏立康唑谷浓度影响因素分析[J]. 今日药学, 2024, 34(12): 927-932.
[10] 彭敏, 黄攀豪, 邓银华, 等. 造血干细胞移植患者伏立康唑稳态谷浓度监测及其影响因素分析[J]. 中国临床药理学与治疗学, 2021, 26(6): 640-646.
[11] 郭冬杰, 李朋梅, 陈文倩, 等. 伏立康唑对肺移植患者术后他克莫司血药浓度影响的真实世界研究[J]. 中国药房, 2025, 34(20): 2519-2524.
[12] HINZE CA, FUGE J, GROTE-KOSKA D, et al. Factors influencing voriconazole plasma level in intensive care patients[J]. JAC Antimicrob Resist, 2024, 6(2): dlae045.
[13] 孙秀漫, 曾彩芳, 邓忠斌, 等. 肾移植患者伏立康唑血药谷浓度和不良反应的影响因素分析[J]. 中国药房, 2025, 36(18): 2301-2306.
[14] LING J, YANG X, DONG L, et al.Influence of C-reactive protein on the pharmacokinetics of voriconazole in relation to the CYP2C19 genotype: a population pharmacokinetics analysis[J]. Front Pharmacol, 2024, 15: 1455721.
[15] MIAO Q, TANG JT, VAN GELDER T, et al.Correlation of CYP2C19 genotype with plasma voriconazole exposure in South-western Chinese Han patients with invasive fungal infections[J]. Medicine (Baltimore), 2019, 98(3): e14137.
[16] ALLEGRA S, DE FRANCIA S, DE NICOLO A, et al.Effect of gender and age on voriconazole trough concentrations in Italian adult patients[J]. Eur J Drug Metab Pharmacokinet, 2020, 45(3): 405-412.
[17] DU YX, ZHU YX, LI L, et al.Interaction of age and CYP2C19 genotypes on voriconazole steady-state trough concentration in Chinese patients[J]. Pharmacogenet Genomics, 2024, 34(6): 191-198.
[18] 中华医学会肝病学分会重型肝病与人工肝学组, 中华医学会感染病学分会肝衰竭与人工肝学组. 肝衰竭诊治指南 (2024年版)[J]. 临床肝胆病杂志, 2024, 40(12): 2371-2387.
[19] RAKHSHAN A, RAHMATI KB, SAFFAEI A, et al.Hepatotoxicity induced by azole antifungal agents: a review study[J]. Iran J Pharm Res, 2023, 22(1): e130336.
[20] NASHIMOTO S, SUGAWARA M, TAKEKUMA Y.Optimization of voriconazole dosage via population pharmacokinetic analysis based on the albumin-bilirubin (ALBI) score of patients with liver dysfunction[J]. J Infect Chemother, 2025, 31(8): 102766.