A Large Sample Retrospective Study on the Distinction of Voriconazole Concentration in Asian Patients from Different Clinical Departments

Zhao, Yunping; Xiao, Chen-Lin; Hou, Jingjing; Wu, Jia‐Min; Xiao, Yiwen; Zhang, Bikui; Sandaradura, Indy; Yan, Miao

doi:10.3390/ph14121239

Cited by 8 publications

(7 citation statements)

References 51 publications

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“…Since the metabolism of voriconazole is regulated by liver enzymes ( Zhong et al, 2018 ), its overexposure may occur in patients with liver damage. Published studies demonstrated that reduced voriconazole elimination is significantly associated with impaired liver function, as indicated by elevated alanine transaminase ( Zhao et al, 2021b ), aspartate transaminase ( Li et al, 2017 ), direct bilirubin ( Zhao Y. C et al, 2021 ) and international normalized ratio levels ( Zhao et al, 2021a ).…”

Section: Discussionmentioning

confidence: 99%

Impact of extracorporeal membrane oxygenation on voriconazole plasma concentrations: A retrospective study

Chen

et al. 2022

Front. Pharmacol.

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Aims: We aimed to assess the impact of extracorporeal membrane oxygenation (ECMO) on voriconazole exposure.Methods: Adult critically ill patients with or without ECMO support receiving intravenous voriconazole therapy were included in this retrospective study conducted in a tertiary referral intensive care unit. The first therapeutic drug monitoring (TDM) results of voriconazole in ECMO patients and non-ECMO patients were collected, and the prevalence of subtherapeutic concentrations was analyzed. Multivariate analyses were performed to evaluate the effect of ECMO on voriconazole exposure.Results: A total of 132 patients (including 66 patients with ECMO support) were enrolled and their respective first voriconazole trough concentrations (Cmin) were recorded. The median Cmin of the ECMO group and the non-ECMO group was 1.9 (1.4–4.4) and 4.4 (3.2–6.9) mg/L, respectively (p = 0.000), and the proportion of the two groups in subtherapeutic concentrations range (<2 mg/L) was 51.5% and 7.6%, respectively (p = 0.000). Multiple linear regression analysis of voriconazole Cmin identified that the use of ECMO and coadministration of glucocorticoids were associated with significantly reduced concentrations, while increasing SOFA score and increasing daily dose were associated with significantly increased concentrations. The model accounted for 32.2% of the variability of voriconazole Cmin. Furthermore, binary logistic regression demonstrated that the use of ECMO was an independent risk factor (OR = 7.78, p = 0.012) for insufficient voriconazole exposure.Conclusion: Our findings showed that, in addition to the known drug interactions, ECMO is a significant covariable affecting voriconazole exposure. In addition, SOFA score was identified as a factor associated with increased voriconazole concentration.

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Section: Discussionmentioning

confidence: 99%

Impact of extracorporeal membrane oxygenation on voriconazole plasma concentrations: A retrospective study

Chen

et al. 2022

Front. Pharmacol.

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“…Conversely, supratherapeutic trough concentrations of VRZ have been linked to adverse events. Compared with other populations (Zhao et al, 2021b;Chen et al, 2022), the initial exposure of VRZ in patients with liver dysfunction appears to be higher. With decreased liver function, the metabolism and excretion of drug are slowed down and VRZ can easily accumulate (Verbeeck, 2008;Gonzalez et al, 2014).…”

Section: Discussionmentioning

confidence: 62%

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

Zhao,

Liu,

Xiao

et al. 2024

Front. Pharmacol.

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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.

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“…The TBIL level was associated with VCZ clearance in IFI patients with liver dysfunction ( Tang et al, 2021 ). TBIL level was also considered an independent factor influencing VCZ C 0 ( Cheng et al, 2020 ; Zeng et al, 2020 ; Zhao Y. et al, 2021 ). However, our results showed that levels of DBIL but not TBIL influenced VCZ C 0 and C 0 /C N .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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Background: Voriconazole (VCZ) metabolism is influenced by many factors. Identifying independent influencing factors helps optimize VCZ dosing regimens and maintain its trough concentration (C0) in the therapeutic window.Methods: We conducted a prospective study investigating independent factors influencing VCZ C0 and the VCZ C0 to VCZ N-oxide concentration ratio (C0/CN) 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.Results: A total of 463 VCZ C0 were analyzed from 304 patients. In younger adult patients, the independent factors that influenced VCZ C0 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 C0/CN were IL-6, age, direct bilirubin, and TBA. The TBA level was positively associated with VCZ C0 (ρ = 0.176, p = 0.019). VCZ C0 increased significantly when the TBA levels were higher than 10 μmol/L (p = 0.027). ROC curve analysis indicated that when the TBA level ≥4.05 μmol/L, the incidence of a VCZ C0 greater than 5 μg/ml (95% CI = 0.54–0.74) (p = 0.007) increased. In elderly patients, the influencing factors of VCZ C0 were DBIL, albumin, and estimated glomerular filtration rate (eGFR). The independent factors that affected VCZ C0/CN were eGFR, ALT, γ-glutamyl transferase, TBA, and platelet count. TBA levels showed a positive association with VCZ C0 (ρ = 0.204, p = 0.006) and C0/CN (ρ = 0.342, p < 0.001). VCZ C0/CN increased significantly when TBA levels were greater than 10 μmol/L (p = 0.025). ROC curve analysis indicated that when the TBA level ≥14.55 μmol/L, the incidence of a VCZ C0 greater than 5 μg/ml (95% CI = 0.52–0.71) (p = 0.048) increased.Conclusion: 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.

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A Large Sample Retrospective Study on the Distinction of Voriconazole Concentration in Asian Patients from Different Clinical Departments

Cited by 8 publications

References 51 publications

Impact of extracorporeal membrane oxygenation on voriconazole plasma concentrations: A retrospective study

Impact of extracorporeal membrane oxygenation on voriconazole plasma concentrations: A retrospective study

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

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

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