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Population Pharmacokinetics and Dosing Simulation of Vancomycin Administered by Continuous Injection in Critically Ill Patient

加药 肾脏替代疗法 医学 万古霉素 药代动力学 肾功能 重症监护室 人口 装载剂量 分配量 剂量 败血症 病危 药效学 重症监护医学 麻醉 内科学 金黄色葡萄球菌 生物 细菌 环境卫生 遗传学
作者
Romain Garreau,Benoît Falquet,Lisa Mioux,Laurent Bourguignon,Tristan Ferry,Michel Tod,Florent Wallet,Arnaud Friggeri,Jean‐Christophe Richard,Sylvain Goutelle
出处
期刊:Antibiotics [Multidisciplinary Digital Publishing Institute]
卷期号:10 (10): 1228-1228 被引量:9
标识
DOI:10.3390/antibiotics10101228
摘要

Background: Vancomycin is widely used for empirical antimicrobial therapy in critically ill patients with sepsis. Continuous infusion (CI) may provide more stable exposure than intermittent infusion, but optimal dosing remains challenging. The aims of this study were to perform population pharmacokinetic (PK) analysis of vancomycin administered by CI in intensive care unit (ICU) patients to identify optimal dosages. Methods: Patients who received vancomycin by CI with at least one measured concentration in our center over 16 months were included, including those under continuous renal replacement therapy (CRRT). Population PK was conducted and external validation of the final model was performed in a dataset from another center. Simulations were conducted with the final model to identify the optimal loading and maintenance doses for various stages of estimated creatinine clearance (CRCL) and in patients on CRRT. Target exposure was defined as daily AUC of 400–600 mg·h/L on the second day of therapy (AUC24–48 h). Results: A two-compartment model best described the data. Central volume of distribution was allometrically scaled to ideal body weight (IBW), whereas vancomycin clearance was influenced by CRRT and CRCL. Simulations performed with the final model suggested a loading dose of 27.5 mg/kg of IBW. The maintenance dose ranged from 17.5 to 30 mg/kg of IBW, depending on renal function. Overall, simulation showed that 55.8% (95% CI; 47–64%) of patients would achieve the target AUC with suggested dosages. Discussion: A PK model has been validated for vancomycin administered by CI in ICU patients, including patients under CRRT. Our model-informed precision dosing approach may help for early optimization of vancomycin exposure in such patients.
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