Therapeutic Drug Monitoring of Voriconazole: Comparison of Bioassay with High-Performance Liquid Chromatography

Badiee, Parisa; Hashemizadeh, Zahra; Montaseri, Hashem

doi:10.5812/jjm.45645

Cited by 8 publications

(12 citation statements)

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“…Its administration in therapeutic doses leads to extremely varied serum levels from patient to patient, and even in the same patient (16). The voriconazole serum concentration (measured by high-performance liquid chromatography [HPLC] or bioassay methods) plays an important role in patient outcomes (17). The present study investigated the factors associated with the variability of voriconazole serum concentrations.…”

Section: Discussionmentioning

confidence: 99%

Observational Study of Associations between Voriconazole Therapeutic Drug Monitoring, Toxicity, and Outcome in Liver Transplant Patients

Hashemizadeh

Badiee

Malekhoseini

et al. 2017

Antimicrob Agents Chemother

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The aim of this study was to investigate the variability of the voriconazole plasma level and its relationships with clinical outcomes and adverse events among liver transplant recipients to optimize the efficacy and safety of their treatment. Liver transplant recipients treated with voriconazole were included, and voriconazole trough levels were quantified by a validated high-performance liquid chromatography method. Cytochrome P450 genotypes for CYP2C19 were evaluated in allograft liver tissues. A total of 832 voriconazole trough levels from 104 patients were measured. Proven, probable, and possible invasive fungal infections were reported for 8/104 (7.7%), 42/104 (40.4%), and 54/104 (51.9%) patients, respectively. Receiver operating characteristic (ROC) curve analysis indicated that trough concentrations of ≥1.3 μg/ml minimized the incidence of treatment failure (95% confidence interval [CI], 0.68 to 0.91 μg/ml) ( < 0.001) and that those of <5.3 μg/ml minimized the incidence of any adverse events (95% CI, 0.83 to 0.97 μg/ml) ( < 0.001). Voriconazole trough levels were significantly higher for heterozygous extensive metabolizers, poor metabolizers, and individuals receiving coadministration with proton pump inhibitors. For ultrarapid metabolizers, oral administration of voriconazole, and concomitant use of glucocorticoids, voriconazole blood concentrations were significantly reduced. Furthermore, there was no statistically significant association of patient age, weight, or gender or coadministration of tacrolimus and cyclosporine with the voriconazole trough level. In conclusion, the results of our analysis indicate large inter- and intraindividual variabilities of voriconazole concentrations in liver transplant recipients. Voriconazole trough concentrations of ≥1.3 μg/ml and <5.3 μg/ml are optimal for treatment and for minimization of adverse events. Optimization of drug efficacy and safety requires the use of rational doses for voriconazole therapy.

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Section: Discussionmentioning

confidence: 99%

Observational Study of Associations between Voriconazole Therapeutic Drug Monitoring, Toxicity, and Outcome in Liver Transplant Patients

Hashemizadeh

Badiee

Malekhoseini

et al. 2017

Antimicrob Agents Chemother

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“…The possibility of VCZ toxicity raised, and VCZ dose adjustment (30% dose reduction) was achieved 5 days later. The patient underwent routine VCZ therapeutic dose monitoring (TDM) [ 17 ]. The VCZ C trough levels were much higher than the expected therapeutic range (VCZ therapeutic reference range: 1.0-5.5 mg/L [ 18 , 19 ]) a few days after the onset of treatment.…”

Section: Case Reportmentioning

confidence: 99%

Generalized exfoliative skin rash as an early predictor of supratherapeutic voriconazole trough levels in a leukemic child: A case report

Amanati¹,

Badiee²,

Lotfi³

et al. 2020

CMM

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Background and Purpose: Skin rashes, mostly seen in children and adolescents, are considered among the most common side effects of azole antifungals. Although therapeutic concentrations of voriconazole (VCZ) have been documented for infected skin, there is no evidence specifying whether specific dermatologic side effects could predict high VCZ serum concentration, especially in high-risk leukemic children.Case report: Herein, we report a unique skin side effect of VCZ in a 5-year-old boy with T-cell acute lymphoblastic leukemia (ALL) referred to Amir Medical Oncology Center in Shiraz, Iran. The patient experienced erythroderma and macular rashes shortly after VCZ consumption, leading to generalized exfoliative skin rashes. Concurrent to these skin manifestations, VCZ serum concentration reached the supratherapeutic levels despite the recommended VCZ doses. As a result, VCZ was withheld, and the patient was treated with caspofungin. The lesions were resolved gradually within 2 weeks, and the patient successfully completed his treatment course with caspofungin. Conclusion: The unique case presented in this study emphasizes the need for a high index of suspicion for VCZ toxicity in any patient with atypical dermatologic manifestations, especially generalized exfoliative skin rashes. Based on this report, VCZ supratherapeutic concentration could be predicted early in the course of treatment. Additional therapeutic dose monitoring should be considered to establish a confirmatory diagnosis. It is required to further investigate the toxic effect of high VCZ concentration on the skin epithelium.

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“…VRZ is the first choice for invasive aspergillosis treatment [1,8]. e oral bioavailability, protein binding, and tissue penetration of VRZ are 96%, 58%, and 2-4.6 L/kg, respectively [9]. VRZ is metabolized by hepatic CYP450 isoenzymes [2,6] and has complicated and nonlinear pharmacokinetic characteristics [2].…”

Section: Introductionmentioning

confidence: 99%

“…e plasma concentration of this drug is unpredictable and varies within and between individuals [10] regardless of the route of administration [11]. is variability is influenced by many factors such as age, sex, body mass index (BMI), polymorphism of CYP2C19, drug-drug interaction, and underlying diseases [2,9,12], which leads to clinical implication [8]. As a result, therapeutic drug monitoring (TDM) is necessary to minimize toxicity and optimize efficacy [3,5].…”

Section: Introductionmentioning

confidence: 99%

“…Low VRZ trough levels (<1 μg/ ml) are correlated with therapeutic failure. High VRZ trough levels (>5.5 μg/ml) are associated with toxicities including skin rash and photosensitivity reaction, visual disturbance, hallucination, hepatotoxicity, and central nervous system (CNS) events [7][8][9]12]. Since TDM of VRZ plays an important role in better evaluation of efficacy and toxicity of treatment, determination of the drug level may be of clinical significance.…”

Section: Introductionmentioning

confidence: 99%

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Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis

Yousefian

Dastan

Marjani

et al. 2021

Canadian Journal of Infectious Diseases and Medical Microbiolog

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Purpose. Invasive aspergillosis is a prevalent fungal disease, especially in Asian countries with a high mortality rate. Voriconazole (VRZ) is the first choice for invasive aspergillosis treatment. Plasma concentration of this drug is unpredictable and varies among individuals. This variability is influenced by many factors leading to clinical implication. Therapeutic drug monitoring (TDM) may have a crucial role in the patients’ treatment process. The HPLC method provides sufficient specificity and sensitivity for plasma VRZ concentration determination for TDM purposes of this drug. Methods. Patients who initiated oral or intravenous VRZ for invasive aspergillosis were enrolled in this study. Demographic characteristics and clinical data, outcome, and adverse effects were documented. For each patient, the plasma sample was collected under steady-state condition and analyzed using a validated HPLC method. Results. A total of 22 measurements were performed. Fifty percent of patients were out of the therapeutic range. From them, 27.27% and 22.73% were in subtherapeutic and supratherapeutic ranges (<1 μg/mL and >5.5 μg/mL), respectively. There was a significant correlation between VRZ plasma concentration and treatment outcomes ( P = 0.022 ). Treatment failure was five times higher than treatment success in those in the subtherapeutic range. Adverse effects were observed more frequently in patients with supratherapeutic concentrations compared to those with non-supratherapeutic levels. Furthermore, the mortality rate in patients experiencing treatment failure was 2.17 times higher than those with treatment success. Conclusions. TDM of VRZ plays an important role in better evaluation of efficacy and toxicity during treatment. Therefore, determination of the drug level may be of clinical significance.

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Therapeutic Drug Monitoring of Voriconazole: Comparison of Bioassay with High-Performance Liquid Chromatography

Abstract: Background: Voriconazole is a triazole antifungal agent with considerable inter and intra-individual variability in plasma concentrations. Therapeutic drug monitoring of voriconazole plays an important role in optimizing the efficacy and safety of the drug in patients.

Cited by 8 publications

References 30 publications

Observational Study of Associations between Voriconazole Therapeutic Drug Monitoring, Toxicity, and Outcome in Liver Transplant Patients

Observational Study of Associations between Voriconazole Therapeutic Drug Monitoring, Toxicity, and Outcome in Liver Transplant Patients

Generalized exfoliative skin rash as an early predictor of supratherapeutic voriconazole trough levels in a leukemic child: A case report

Determination of Voriconazole Plasma Concentration by HPLC Technique and Evaluating Its Association with Clinical Outcome and Adverse Effects in Patients with Invasive Aspergillosis

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