Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 4:14:1323755.
doi: 10.3389/fphar.2023.1323755. eCollection 2023.

Enhancing voriconazole therapy in liver dysfunction: exploring administration schemes and predictive factors for trough concentration and efficacy

Yichang Zhao #  1   2 , Huaiyuan Liu #  1   3 , Chenlin Xiao  1   2 , Jingjing Hou  1   2 , Bikui Zhang  1   2 , Jiakai Li  1   2 , Min Zhang  4 , Yongfang Jiang  4 , Indy Sandaradura  5   6 , Xuansheng Ding  3 , Miao Yan  1   2
Affiliations

Enhancing voriconazole therapy in liver dysfunction: exploring administration schemes and predictive factors for trough concentration and efficacy

Yichang Zhao et al. Front Pharmacol. .

Abstract

Introduction: The application of voriconazole in patients with liver dysfunction lacks pharmacokinetic data. In previous study, we proposed to develop voriconazole dosing regimens for these patients according to their total bilirubin, but the regimens are based on Monte Carlo simulation and has not been further verified in clinical practice. Besides, there are few reported factors that significantly affect the efficacy of voriconazole. Methods: We collected the information of patients with liver dysfunction hospitalized in our hospital from January 2018 to May 2022 retrospectively, including their baseline information and laboratory data. We mainly evaluated the efficacy of voriconazole and the target attainment of voriconazole trough concentration. Results: A total of 157 patients with liver dysfunction were included, from whom 145 initial and 139 final voriconazole trough concentrations were measured. 60.5% (95/157) of patients experienced the adjustment of dose or frequency. The initial voriconazole trough concentrations were significantly higher than the final (mean, 4.47 versus 3.90 μg/mL, p = 0.0297). Furthermore, daily dose, direct bilirubin, lymphocyte counts and percentage, platelet, blood urea nitrogen and creatinine seven covariates were identified as the factors significantly affect the voriconazole trough concentration. Binary logistic regression analysis revealed that the lymphocyte percentage significantly affected the efficacy of voriconazole (OR 1.138, 95% CI 1.016-1.273), which was further validated by the receiver operating characteristic curve. Conclusion: The significant variation in voriconazole trough concentrations observed in patients with liver dysfunction necessitates caution when prescribing this drug. Clinicians should consider the identified factors, particularly lymphocyte percentage, when dosing voriconazole in this population.

Keywords: efficacy; liver dysfunction; therapeutic drug monitoring; trough concentration; voriconazole.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The box chart of initial and final voriconazole trough concentrations,*p < 0.05.
FIGURE 2
FIGURE 2
The correlation analysis between seven covariates and voriconazole trough concentrations. (A) Daily dose. (B) Lymphocyte counts. (C) Lymphocyte percentage. (D) Platelet counts. (E) Direct bilirubin. (F) Blood urea nitrogen. (G) Creatinine.
FIGURE 3
FIGURE 3
(A) The distribution of initial voriconazole trough concentrations grouped by CYP2C19 phenotype. (B) The distribution of initial voriconazole trough concentration grouped by baseline Child-Pugh class. (C) The distribution of final voriconazole trough concentration grouped by final Child-Pugh class. Dashed line: 1 and 5.5, respectively. *p < 0.05, **p < 0.01.
FIGURE 4
FIGURE 4
The receiver operating characteristic curve of lymphocyte percentage predicting the efficacy of voriconazole. AUC: Area Under the Curve.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Brüggemann R. J. M., Alffenaar J.-W. C., Blijlevens N. M. A., Billaud E. M., Kosterink J. G. W., Verweij P. E., et al. (2009). Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Clin. Infect. Dis. 48 (10), 1441–1458. 10.1086/598327 - DOI - PubMed
    1. Chen J., Wu Y., He Y., Feng X., Ren Y., Liu S. (2022). Combined effect of CYP2C19 genetic polymorphisms and C-reactive protein on voriconazole exposure and dosing in immunocompromised children. Front. Pediatr. 10, 846411. 10.3389/fped.2022.846411 - DOI - PMC - PubMed
    1. Chen K., Zhang X., Ke X., Du G., Yang K., Zhai S. (2018). Individualized medication of voriconazole: a practice guideline of the division of therapeutic drug monitoring, Chinese pharmacological society. Ther. Drug Monit. 40 (6), 663–674. 10.1097/ftd.0000000000000561 - DOI - PMC - PubMed
    1. Chen W., Xie H., Liang F., Meng D., Rui J., Yin X., et al. (2015). Population pharmacokinetics in China: the dynamics of intravenous voriconazole in critically ill patients with pulmonary disease. Biol. Pharm. Bull. 38 (7), 996–1004. 10.1248/bpb.b14-00768 - DOI - PubMed
    1. Dolton M. J., Ray J. E., Chen S. C., Ng K., Pont L. G., McLachlan A. J. (2012). Multicenter study of voriconazole pharmacokinetics and therapeutic drug monitoring. Antimicrob. Agents Chemother. 56 (9), 4793–4799. 10.1128/aac.00626-12 - DOI - PMC - PubMed

LinkOut - more resources