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教学医院中基于治疗药物监测的阿米卡星群体药代动力学研究

Therapeutic Drug Monitoring-Based Population Pharmacokinetics of Amikacin in Patients at a Teaching Hospital.

作者信息

Steffens Nadine Arnold, Zimmermann Estevan Sonego, Azeredo Francine Johansson, Linden Rafael, Finatto Luis Junior, Hahn Roberta Zilles, Schwarzbold Alexandre Vargas, Pacheco Liliane Souto, Brucker Natália

机构信息

Graduate Program in Pharmaceutical Sciences, Federal University of Santa Maria, Av. Roraima, 1000, Camobi, Santa Maria 97105-900, RS, Brazil.

Center for Pharmacometrics and Systems Pharmacology, University of Florida, Gainesville, FL 32827, USA.

出版信息

Antibiotics (Basel). 2025 May 22;14(6):531. doi: 10.3390/antibiotics14060531.

Abstract

: Amikacin is still an essential antimicrobial to treat life-threatening infections, including multidrug-resistant microorganisms. The effectiveness of treatment has been correlated with the Cmax/MIC ratio, with a ratio of 8 being recommended, which is difficult to reach in some patients. Appropriate antibiotic exposure is important for knowing the disposition of the drug in the population. : We aimed to integrate therapeutic drug monitoring and a populational pharmacokinetic model to assess an optimal dose regimen and respective plasma exposure. : Plasma levels of amikacin in peaks and troughs were determined by LC-MS/MS. The pharmacokinetic parameter was estimated to use nonlinear mixed effect modeling in Monolix software. The probability of target attainment was also determined using the Simulx™ software. : A total of 39 patients were enrolled. A one-compartment model with proportional error model best described amikacin pharmacokinetic parameters, providing a Cl of 1.49 L/h and Vc of 23.18 L. The model developed could characterize the pharmacokinetic profile in Brazilian patients who underwent therapeutic drug monitoring. : Amikacin therapeutic drug monitoring should be associated with population pharmacokinetic analysis in dose optimization and individualization, helping maintain appropriate drug exposure in special populations such as critically ill patients. This strategy may contribute to enhancing clinical outcomes.

摘要

阿米卡星仍然是治疗包括多重耐药微生物在内的危及生命感染的重要抗菌药物。治疗效果与血药峰浓度/最低抑菌浓度(Cmax/MIC)比值相关,推荐比值为8,但在一些患者中难以达到。了解药物在人群中的处置情况时,适当的抗生素暴露很重要。我们旨在整合治疗药物监测和群体药代动力学模型,以评估最佳剂量方案和相应的血浆暴露情况。通过液相色谱-串联质谱法(LC-MS/MS)测定阿米卡星的血药峰浓度和谷浓度。使用Monolix软件中的非线性混合效应模型估计药代动力学参数。还使用Simulx™软件确定目标达成概率。共纳入39例患者。具有比例误差模型的单室模型最能描述阿米卡星的药代动力学参数,清除率(Cl)为1.49 L/h,中央室容积(Vc)为23.18 L。所建立的模型能够表征接受治疗药物监测的巴西患者的药代动力学特征。在剂量优化和个体化过程中,阿米卡星治疗药物监测应与群体药代动力学分析相结合,有助于在重症患者等特殊人群中维持适当的药物暴露。该策略可能有助于改善临床结局。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8614/12189896/7e4254019aa2/antibiotics-14-00531-g001.jpg

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