A retrospective, multicenter study of voriconazole trough concentrations and safety in patients with Child-Pugh class C cirrhosis

Wang, T.; Yan, Miao; Tang, Dan; Xue, Liang; Zhang, Tianlong; Zhu, Li; Wang, X.; Dong, Yuzhu

doi:10.1111/jcpt.12724

Cited by 23 publications

(21 citation statements)

References 15 publications

(29 reference statements)

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“…17,23,33 The consequences of increased voriconazole absorption and reduced voriconazole metabolism and/or excretion result in increased overall voriconazole plasma concentration which could lead to increased risk of adverse events, especially with repeated administrations. Previous studies 34,35 showed that the recommended dose and halved maintenance dose in patients with Child-Pugh class B and C cirrhosis may be inappropriate. Therefore, lower doses or longer administration intervals should be considered to reduce the risk of toxicity.…”

Section: Discussionmentioning

confidence: 99%

“…A therapeutic concentration range between 0.5 mg/L and 5 mg/L has been recommended in the Chinese Practice Guideline for Individualized Medication of voriconazole to improve treatment outcome and minimize the risk of adverse events. Previous studies suggested that voriconazole trough concentration should be monitored routinely at the initiation of therapy to avoid adverse events, because voriconazole‐related adverse events usually occurred in the first week after voriconazole treatment.…”

Section: Discussionmentioning

confidence: 99%

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Identifying factors affecting the pharmacokinetics of voriconazole in patients with liver dysfunction: A population pharmacokinetic approach

Tang

Song

Yan

et al. 2019

Basic Clin Pharma Tox

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Voriconazole is a broad‐spectrum antifungal agent commonly used to treat invasive fungal infections. Voriconazole has significant intraindividual and interindividual pharmacokinetics variability in different patient populations. Pharmacokinetic data of voriconazole in patients with liver dysfunction were limited. The aims of this study were to evaluate the population pharmacokinetics of voriconazole in patients with liver dysfunction and to identify the factors that affect voriconazole pharmacokinetics. A total of 166 samples taken from 57 patients with liver dysfunction were included in the study. A one‐compartment pharmacokinetic model with first‐order absorption and elimination was used to describe the data. Voriconazole clearance (CL) was 0.58 L/h, the volume of distribution (Vd) was 134 L, and oral bioavailability (F) was 80.8%. This study showed that platelet count was significantly associated with voriconazole pharmacokinetic parameters. CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. Voriconazole CL was significantly decreased in patients with liver dysfunction. This study provides useful pharmacokinetics information for patients with liver dysfunction while highlighting the value of therapeutic drug monitoring in adjusting doses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identifying factors affecting the pharmacokinetics of voriconazole in patients with liver dysfunction: A population pharmacokinetic approach

Tang

Song

Yan

et al. 2019

Basic Clin Pharma Tox

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“…The same authors conducted another study including solely patients with Child–Pugh Class C cirrhosis [103]. Patients were allocated to two groups, according to the dosage schedule of voriconazole’s maintenance dose.…”

Section: Antifungal Agentsmentioning

confidence: 99%

“…Further analysis revealed that the increasing C min of voriconazole was associated with increasing incidence of AEs, although no statistical significance was found. It was suggested that in patients with Child–Pugh Class C cirrhosis the halved maintenance dose is probably inappropriate, and that lower dosage should be considered in conjunction with early TDM [103].…”

Section: Antifungal Agentsmentioning

confidence: 99%

Pre-Existing Liver Disease and Toxicity of Antifungals

Spernovasilis

Kofteridis

2018

JoF

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Pre-existing liver disease in patients with invasive fungal infections further complicates their management. Altered pharmacokinetics and tolerance issues of antifungal drugs are important concerns. Adjustment of the dosage of antifungal agents in these cases can be challenging given that current evidence to guide decision-making is limited. This comprehensive review aims to evaluate the existing evidence related to antifungal treatment in individuals with liver dysfunction. This article also provides suggestions for dosage adjustment of antifungal drugs in patients with varying degrees of hepatic impairment, after accounting for established or emerging pharmacokinetic–pharmacodynamic relationships with regard to antifungal drug efficacy in vivo.

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“…However, there is no recommended voriconazole regimen for patients with Child-pugh C cirrhosis (CP-C). Meanwhile, our previous study demonstrated that the halved dose still leads to a supratherapeutic level in the majority of cirrhotic patients, with a voriconazole C min of 4.02 ± 2.00 mg/L (14, 15).…”

Section: Introductionmentioning

confidence: 97%

Pharmacokinetics Modeling and Simulation of Voriconazole Dosing and Safety in Patients with Liver Cirrhosis

Wang

Yan

Tang

et al. 2019

Preprint

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26Voriconazole is used to treat invasive fungal disease and the optimal dose regimens 27 are still unknown in cirrhotic Patients. The aim of this study was to determine the 28 safety, to describe pharmacokinetics characteristics, and to optimize dosage regimens 29 of voriconazole in cirrhotic patients. Data pertaining to voriconazole were collected 30 retrospectively and analyzed using a population pharmacokinetics model. A total of 31 219 trough concentrations (C min ) from 120 patients were analyzed. 32 Voriconazole-related adverse events developed in 29 patients, with 69.0% of AEs 33 developing within the first week after voriconazole treatment. The threshold C min for 34 AEs was 5.12 mg/L. A one-compartment model with first-order absorption and 35 elimination adequately described the data. The Child-Pugh class was the only 36 covariate in final model. Voriconazole clearance in patients with Child-pugh A and B 37 cirrhosis (CP-A/CP-B) and Child-pugh C cirrhosis (CP-C) were 1.79 L/h and 0.99 L/h, 38 respectively, the volume of distribution was 159.6 L, and the oral bioavailability was 39 91.8%. The elimination half-life was significantly extended for up to 61.8 -111.7 h in 40 cirrhotic patients. Model-based simulations showed that the appropriate maintenance 41 doses are 75 mg/12 h and 150 mg/24 h intravenously or orally for CP-A/CP-B 42 patients, and 50 mg/12 h and 100 mg/24 h intravenously or orally for CP-C patients. 43The results support voriconazole maintenance doses in LC patients should be reduced 44 to one-fourth for CP-C patients and to one-third for CP-A/CP-B patients compared to 45 that for patients with normal liver function. Monitoring C min early could be a useful 46 strategy to ensure the safety. 47

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A retrospective, multicenter study of voriconazole trough concentrations and safety in patients with Child-Pugh class C cirrhosis

Cited by 23 publications

References 15 publications

Identifying factors affecting the pharmacokinetics of voriconazole in patients with liver dysfunction: A population pharmacokinetic approach

Identifying factors affecting the pharmacokinetics of voriconazole in patients with liver dysfunction: A population pharmacokinetic approach

Pre-Existing Liver Disease and Toxicity of Antifungals

Pharmacokinetics Modeling and Simulation of Voriconazole Dosing and Safety in Patients with Liver Cirrhosis

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