External evaluation of population pharmacokinetic models for voriconazole in Chinese adult patients with hematological malignancy

Huang, Weikun; Zheng, You; Huang, Huiping; Chen, Yu; Liu, Maobai; Chaphekar, Nupur; Wu, Xuemei

doi:10.1007/s00228-022-03359-2

Cited by 8 publications

(11 citation statements)

References 58 publications

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“…Furthermore, the data reveals that F 20 represents 32.8% of the total, whereas F 30 accounts for 50.8%, indicating an acceptable level of performance. 22,23 The final model exhibited commendable precision and accuracy overall, aligning well with the aforementioned evaluation criteria.…”

Section: Model Evaluationsupporting

confidence: 66%

“…The evaluation criteria were MPE ≤ ±15%, MAPE ≤ 30%, F 20 > 35%, and F 30 > 50%. 22,23 Monte Carlo Simulations of Dosage Regimens The Monte Carlo simulations, consisting of 10,000 replicates, were performed using Crystal Ball 11.1.2.4 (Oracle, Redwood Shores, CA, USA), based on the parameter estimates derived from the final model. Each observed individual's set of relevant parameters was sampled with replacements to comprise the simulation datasets.…”

Section: Model Evaluationmentioning

confidence: 99%

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Population Pharmacokinetics of Voriconazole and Dose Optimization in Elderly Chinese Patients

Wang,

Shen,

et al. 2023

The Journal of Clinical Pharma

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Voriconazole is commonly recommended as a first‐line therapy for invasive aspergillosis infections. The elderly patients are susceptible to infectious diseases owing to their decreased physical function and immune system. Our study aims to establish a population‐based pharmacokinetic model for receiving intravenous voriconazole of elderly patients, and to optimize dosing protocols through a simulated approach. An accurate fit to the concentration‐time profile of voriconazole was achieved by employing a one‐compartment model featuring first‐order elimination. The typical clearance rate of voriconazole was found to be 3.22 L/h, with a typical volume of distribution of 194 L. The covariate analysis revealed that albumin (ALB), gamma glutamyl transpeptidase, and direct bilirubin had significant impacts on voriconazole clearance. Additionally, the body weight was found to be associated with the volume. Individualized dosing regimens were recommended for different ALB levels based on population PK model prediction. The proposed dosing regimens could provide a rationale for dosage individualization, improve the clinical outcomes and minimize drug‐related toxicities.This article is protected by copyright. All rights reserved

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Section: Model Evaluationsupporting

confidence: 66%

Section: Model Evaluationmentioning

confidence: 99%

Population Pharmacokinetics of Voriconazole and Dose Optimization in Elderly Chinese Patients

Wang,

Shen,

et al. 2023

The Journal of Clinical Pharma

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“…The daily loading and maintenance doses of isavuconazole, posaconazole, and voriconazole were 600 mg/200 mg, 600 mg/300 mg, and 800 mg/400 mg, respectively, whether administrated orally or intravenously. The dose of L-AmB was administrated at 5 mg/kg, and the mean body weight (60 kg) of Chinese patients with hematologic malignancies or hematopoietic stem cell transplantation was used to calculate the total daily dose of L-AmB [22,23].…”

Section: Treatment Regimen and Durationmentioning

confidence: 99%

Pharmacoeconomic evaluation of isavuconazole, posaconazole and voriconazole in the treatment of invasive fungal infection: initial therapy prior to pathogen differential diagnosis in China

Han

et al. 2023

Preprint

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Background Invasive fungal infections (IFIs) is associated with high mortality and a substantial economic burden. For high-risk patients, fever drive or diagnostic drive therapy is usually initiated prior to the differential diagnosis of the pathogen. This study evaluated the cost-effectiveness of isavuconazole, posaconazole, versus voriconazole in the treatment of invasive fungal infections from the perspective of the Chinese healthcare system, informing healthcare decision-making and resource allocation.Methods A decision analytic model was constructed using TreeAge Pro 2011 software to evaluate the cost-effectiveness of the entire disease course. We assumed that the prevalence of mucormycosis in the patients entering the model was 7.8%. Efficacy, cost, adverse events, and other data included in the model were mainly derived from clinical studies, published literature, and publicly available databases. The primary outcomes of the model output were total cost, quality-adjusted life years (QALYs), life years (Lys), and incremental cost-effectiveness ratio (ICER). The willing-to-pay (WTP) threshold was defined as one to three times China’s GDP per capita in 2022. One-way sensitivity analysis and probability sensitivity analysis were used to determine the robustness of the model. At the same time, the cost-effectiveness of three triazole antifungal agents under a broader range of mucormycosis prevalence, when voriconazole was covered by medical insurance reimbursement, and after the price reduction of posaconazole was discussed.Results Base-case analysis showed that isavuconazole had greater efficacy (+ 0.38 LYs and + 0.31 QALYs) than voriconazole; ICER was $15,702.46 /QALY, well below the WTP threshold ($38,223 /QALY). However, posaconazole did not provide a significant economic advantage over voriconazole (ICER $64,466.57 /QALY). One-way sensitivity analysis found that ICER was highly sensitive to the mortality of patients with invasive aspergillus infection. In the probabilistic sensitivity analysis, when the WTP threshold was $38223 /QALY, the probability of isavuconazole being cost-effective was 72.9%. The scenario analysis results indicated that posaconazole would become cost-effective when the price was reduced by 15% or the prevalence of mucormycosis was 14%.Conclusions Isavuconazole represents a cost-effective initial option for treating IFIs in high-risk patients prior to the differential diagnosis of pathogens. It will also be economical when a 15% reduction in posaconazole cost is achieved.

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“…Compared with other antifungal drugs, VRC has the lowest discontinuation rate and may represent the best option for patients undergoing HCT 13 . However, VRC has a narrow therapeutic range and complex nonlinear pharmacokinetics; furthermore, multiple factors are known to be associated with the pharmacokinetics of VRC, including age, body weight, liver function, and genetic polymorphisms of the cytochrome P450 (CYP) 2C19 enzyme, all of which complicate the successful therapeutic use of VRC in the pediatric population 14,15 . Of these, CYP2C19 polymorphisms are considered a key determinant of the wide pharmacokinetic (PK) variability of VRC 16 .…”

mentioning

confidence: 99%

“…13 However, VRC has a narrow therapeutic range and complex nonlinear pharmacokinetics; furthermore, multiple factors are known to be associated with the pharmacokinetics of VRC, including age, body weight, liver function, and genetic polymorphisms of the cytochrome P450 (CYP) 2C19 enzyme, all of which complicate the successful therapeutic use of VRC in the pediatric population. 14,15 Of these, CYP2C19 polymorphisms are considered a key determinant of the wide pharmacokinetic (PK) variability of VRC. 16 Low levels of exposure to VRC may result in treatment failure, whereas high levels of exposure may result in adverse neurological effects, hepatotoxicity, and visual impairment.…”

mentioning

confidence: 99%

Optimization of Voriconazole Dosing Regimens Against Aspergillus Species and Candida Species in Pediatric Patients After Hematopoietic Cell Transplantation: A Theoretical Study Based on Pharmacokinetic/Pharmacodynamic Analysis

Xie

Jiang

Qiu

et al. 2023

The Journal of Clinical Pharma

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This study aimed to optimize the dosing regimens of voriconazole (VRC) for pediatric patients after hematopoietic cell transplantation with different cytochrome P450 (CYP) 2C19 phenotypes and body weights, based on pharmacokinetic (PK)/pharmacodynamic (PD) analysis. The PK parameters of VRC were derived from previous literature. Combined with key factors affecting VRC, patients were categorized into 9 subgroups based on different CYP2C19 phenotypes (poor metabolizer/intermediate metabolizer, normal metabolizer, and rapid metabolizer/ultrarapid metabolizer) and typical body weights (15, 40, and 65 kg). Monte Carlo simulation was used to investigate dosing regimens for different groups. The area under the 24‐hour free drug concentration–time curve to the minimum inhibitory concentration (MIC) > 25 was used as the target value for effective treatment. The probability of target achievement and the cumulative fraction of response were determined on the basis of the assumed MICs and MICs distribution frequency of Aspergillus species and Candida species. When the MIC was ≤1 mg/L, 4 mg/kg every 12 hours was sufficient for optimal effects in groups 1‐3 and groups 5 and 6; however, 6 mg/kg every 12 hours was required for group 4, and 8 mg/kg every 12 hours was required for groups 7‐9. In empirical treatment, lower (2‐6 mg/kg every 12 hours) and higher (6‐12 mg/kg every 12 hours) dosing regimens were recommended for Candida spp. and Aspergillus spp., respectively. Our findings will assist in selecting appropriate dosing regimens of VRC for pediatric patients after hematopoietic cell transplantation with different CYP2C19 phenotypes and body weights. Clinically, it is better to continuously adjust the dosing on the basis of the therapeutic drug monitoring.

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External evaluation of population pharmacokinetic models for voriconazole in Chinese adult patients with hematological malignancy

Cited by 8 publications

References 58 publications

Population Pharmacokinetics of Voriconazole and Dose Optimization in Elderly Chinese Patients

Population Pharmacokinetics of Voriconazole and Dose Optimization in Elderly Chinese Patients

Pharmacoeconomic evaluation of isavuconazole, posaconazole and voriconazole in the treatment of invasive fungal infection: initial therapy prior to pathogen differential diagnosis in China

Optimization of Voriconazole Dosing Regimens Against Aspergillus Species and Candida Species in Pediatric Patients After Hematopoietic Cell Transplantation: A Theoretical Study Based on Pharmacokinetic/Pharmacodynamic Analysis

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