Frontiers in cellular and infection microbiology · 2026
Exploratory model-based optimizing isavuconazole dosing regimens for Aspergillus spp. in adult patients according to serum albumin levels: a pharmacokinetic/pharmacodynamic analysis using Monte Carlo simulation.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Wei Xiao-Chen, Zhao Ming-Feng, Lyu Hai-Rong, Xiao Xia
Аннотация
OBJECTIVES: Serum albumin strongly influences isavuconazole pharmacokinetics due to its high plasma protein binding. Hypoalbuminemia, common in critically ill and immunocompromised patients, may cause subtherapeutic concentrations with standard isavuconazole dosage. This study aimed to optimize isavuconazole dosing regimens against Aspergillus spp. in adult patients based on serum albumin levels.
METHODS: A published population pharmacokinetic model of isavuconazole was used to simulate four dosing regimens stratified by serum albumin levels. Monte Carlo simulations calculated probability of target attainment (PTA) and cumulative fraction of response (CFR) based on the area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratios, with separate targets for immunocompetent and immunocompromised patients. PTA or CFR > 90% was considered optimal for a dosing regimen.
RESULTS: Based on PTA analysis for Aspergillus spp. with an MIC of 1 μg/mL, PTAs were 0%, 71.23%, 100%, and 100% in immunocompetent patients with mild hypoalbuminemia and 0%, 0.32%, 100%, and 100% in those with marked hypoalbuminemia for 100 mg, 200 mg, 300 mg, and 400 mg q24h, respectively, whereas in immunocompromised patients PTAs were 0%, 0%, 33.04%, and 100% with mild hypoalbuminemia and 0%, 0%, 0%, and 100% with marked hypoalbuminemia at the same doses, supporting 300 mg q24h for immunocompetent hypoalbuminemic adults and 400 mg q24h for immunocompromised counterparts. Furthermore, the CFR analysis demonstrated that the 200 mg q24h regimen was adequate against A. terreus and A. versicolor. Additionally, the 300 mg q24h regimen was recommended for immunocompetent adult patients with hypoalbuminemia in the treatment of A. fumigatus and A. flavus; conversely, immunocompromised adult patients with hypoalbuminemia necessitated the 400 mg q24h dosage for these pathogens. However, the majority of simulating dosing regimens failed to achieve the desired CFR values against A. niger.
CONCLUSIONS: These PK/PD simulations support isavuconazole dose optimization for hypoalbuminemic adults with aspergillosis and require prospective clinical validation.
METHODS: A published population pharmacokinetic model of isavuconazole was used to simulate four dosing regimens stratified by serum albumin levels. Monte Carlo simulations calculated probability of target attainment (PTA) and cumulative fraction of response (CFR) based on the area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) ratios, with separate targets for immunocompetent and immunocompromised patients. PTA or CFR > 90% was considered optimal for a dosing regimen.
RESULTS: Based on PTA analysis for Aspergillus spp. with an MIC of 1 μg/mL, PTAs were 0%, 71.23%, 100%, and 100% in immunocompetent patients with mild hypoalbuminemia and 0%, 0.32%, 100%, and 100% in those with marked hypoalbuminemia for 100 mg, 200 mg, 300 mg, and 400 mg q24h, respectively, whereas in immunocompromised patients PTAs were 0%, 0%, 33.04%, and 100% with mild hypoalbuminemia and 0%, 0%, 0%, and 100% with marked hypoalbuminemia at the same doses, supporting 300 mg q24h for immunocompetent hypoalbuminemic adults and 400 mg q24h for immunocompromised counterparts. Furthermore, the CFR analysis demonstrated that the 200 mg q24h regimen was adequate against A. terreus and A. versicolor. Additionally, the 300 mg q24h regimen was recommended for immunocompetent adult patients with hypoalbuminemia in the treatment of A. fumigatus and A. flavus; conversely, immunocompromised adult patients with hypoalbuminemia necessitated the 400 mg q24h dosage for these pathogens. However, the majority of simulating dosing regimens failed to achieve the desired CFR values against A. niger.
CONCLUSIONS: These PK/PD simulations support isavuconazole dose optimization for hypoalbuminemic adults with aspergillosis and require prospective clinical validation.