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中性粒细胞减少的肿瘤患者中阿米卡星的治疗药物监测

Therapeutic Drug Monitoring of Amikacin in Neutropenic Oncology Patients.

作者信息

Aquino Maria, Tinoco Maria, Bicker Joana, Falcão Amílcar, Rocha Marília, Fortuna Ana

机构信息

Laboratory of Pharmacology, Faculty of Pharmacy, University of Coimbra, 3000-548 Coimbra, Portugal.

CIBIT-Coimbra Institute for Biomedical Imaging and Translational Research, University of Coimbra, 3000-548 Coimbra, Portugal.

出版信息

Antibiotics (Basel). 2023 Feb 11;12(2):373. doi: 10.3390/antibiotics12020373.

Abstract

Amikacin is the antibiotic of choice for the treatment of Gram-negative infections, namely, those in neutropenic oncology patients. No populational pharmacokinetic studies are currently available reporting amikacin pharmacokinetics in neutropenic oncology patients despite their specific pathophysiological features and treatments. A large-scale retrospective study was herein conducted to specifically investigate the effects that tumor diseases have on the pharmacokinetic parameters of amikacin and identify whether chemotherapy, the lag time between administration of chemotherapy and amikacin, age and renal function contribute to amikacin pharmacokinetics in neutropenic cancer patients. A total of 1180 pharmacokinetic analysis from 629 neutropenic patients were enrolled. The daily dose administered to oncology patients was higher than that administered to non-oncology patients ( < 0.0001). No statistical differences were found in amikacin concentrations, probably because drug clearance was increased in cancer patients ( < 0.0001). Chemotherapy influenced amikacin pharmacokinetics and drug clearance decreased as the lag time enhanced. The elderly group revealed no statistical differences between the doses administered to both the oncology groups, suggesting that the impact of ageing is stronger than chemotherapy. Our research suggests that cancer patients require higher initial doses of amikacin, as well as when chemotherapy is received less than 30 days before amikacin treatment has started.

摘要

阿米卡星是治疗革兰氏阴性菌感染的首选抗生素,即用于治疗中性粒细胞减少的肿瘤患者的感染。尽管中性粒细胞减少的肿瘤患者有其特定的病理生理特征和治疗方法,但目前尚无关于这些患者中阿米卡星药代动力学的群体药代动力学研究报告。本文进行了一项大规模回顾性研究,专门调查肿瘤疾病对阿米卡星药代动力学参数的影响,并确定化疗、化疗与阿米卡星给药之间的间隔时间、年龄和肾功能是否对中性粒细胞减少的癌症患者的阿米卡星药代动力学有影响。共纳入了629例中性粒细胞减少患者的1180次药代动力学分析。肿瘤患者的每日给药剂量高于非肿瘤患者(<0.0001)。阿米卡星浓度未发现统计学差异,可能是因为癌症患者的药物清除率增加(<0.0001)。化疗影响阿米卡星的药代动力学,且随着间隔时间延长药物清除率降低。老年组显示两个肿瘤组给药剂量之间无统计学差异,表明衰老的影响比化疗更强。我们的研究表明,癌症患者需要更高的阿米卡星初始剂量,以及在开始阿米卡星治疗前30天内接受化疗的患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d13b/9952017/ee854ffb90b6/antibiotics-12-00373-g001.jpg

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