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持续肾脏替代疗法对感染性休克患者替加环素血浆浓度的影响:一项前瞻性观察研究。

Influence of continuous renal replacement therapy on the plasma concentration of tigecycline in patients with septic shock: A prospective observational study.

作者信息

Huang Fang, Cao Wen-Xiang, Yan Yu-Ying, Mao Tian-Tian, Wang Xian-Wen, Huang Dan, Qiu Yu-Shuang, Lu Wen-Jie, Li Dong-Jie, Zhuang Yu-Gang

机构信息

Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.

School of Pharmacy, Nanjing Medical University, Nanjing, China.

出版信息

Front Pharmacol. 2023 Mar 9;14:1118788. doi: 10.3389/fphar.2023.1118788. eCollection 2023.

DOI:10.3389/fphar.2023.1118788
PMID:36969878
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10034132/
Abstract

The influence of continuous renal replacement therapy (CRRT) on the steady-state plasma concentration of high-dose tigecycline was investigated in septic shock patients to provide references for drug dosing. In this prospective observational study, 17 septic shock patients presenting with severe infections needing a broad-spectrum antibiotic therapy with high-dose tigecycline (100 mg per 12 h) in the intensive care unit were included and divided into CRRT group ( = 6) or non-CRRT group ( = 11). The blood samples were collected and plasma drug concentration was determined by SHIMADZU LC-20A and SHIMADZU LCMS 8040. The steady-state plasma concentration was compared between groups using unpaired -test. Furthermore, between-groups comparisons adjusted for baseline value was also done using multivariate linear regression model. Peak concentration (C) of tigecycline was increased in CRRT group compared to non-CRRT group, but there were no statistical differences (505.11 ± 143.84 vs 406.29 ± 108.00 ng/mL, -value: 0.129). Trough concentration (C) of tigecycline was significantly higher in CRRT group than in non-CRRT group, with statistical differences (287.92 ± 41.91 vs 174.79 ± 33.15 ng/mL, -value: 0.000, adjusted -value: 0.000). In safety, C was reported to be a useful predictor of hepatotoxicity with a cut-off of 474.8 ng/mL. In our studies, C of all patients in CRRT group was lower than 474.8 ng/mL. The plasma concentration of tigecycline was increased in septic shock patients with CRRT treatment and only C shown statistical differences. No dose adjustment seems needed in the view of hepatotoxicity. https://www.chictr.org.cn/, identifier ChiCTR2000037475.

摘要

在脓毒症休克患者中研究了持续肾脏替代治疗(CRRT)对高剂量替加环素稳态血浆浓度的影响,以为药物给药提供参考。在这项前瞻性观察性研究中,纳入了17例在重症监护病房中因严重感染需要高剂量替加环素(每12小时100mg)进行广谱抗生素治疗的脓毒症休克患者,并将其分为CRRT组(n = 6)或非CRRT组(n = 11)。采集血样并通过岛津LC - 20A和岛津LCMS 8040测定血浆药物浓度。使用非配对t检验比较两组之间的稳态血浆浓度。此外,还使用多元线性回归模型对基线值进行了组间比较调整。与非CRRT组相比,CRRT组中替加环素的峰浓度(Cmax)有所升高,但无统计学差异(505.11±143.84 vs 406.29±108.00 ng/mL,P值:0.129)。CRRT组中替加环素的谷浓度(Cmin)显著高于非CRRT组,有统计学差异(287.92±41.91 vs 174.79±33.15 ng/mL,P值:0.000,调整后P值:0.000)。在安全性方面,据报道Cmax是肝毒性的有用预测指标,临界值为474.8 ng/mL。在我们的研究中,CRRT组所有患者的Cmax均低于474.8 ng/mL。接受CRRT治疗的脓毒症休克患者中替加环素的血浆浓度升高,仅Cmin显示出统计学差异。从肝毒性角度来看似乎无需调整剂量。https://www.chictr.org.cn/,标识符ChiCTR2000037475

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本文引用的文献

1
[Effectiveness of regional citrate anticoagulation in continuous renal replacement therapy].[局部枸橼酸抗凝在连续性肾脏替代治疗中的有效性]
Rev Med Chil. 2022 Mar;150(3):283-288. doi: 10.4067/S0034-98872022000300283.
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Right dose, right now: bedside, real-time, data-driven, and personalised antibiotic dosing in critically ill patients with sepsis or septic shock-a two-centre randomised clinical trial.精准用药:即时、床边、数据驱动和个体化的脓毒症或感染性休克危重症患者抗生素治疗——一项两中心随机临床试验。
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Population Pharmacokinetics of Tigecycline: A Systematic Review.替加环素的群体药代动力学:系统评价。
Drug Des Devel Ther. 2022 Jun 17;16:1885-1896. doi: 10.2147/DDDT.S365512. eCollection 2022.
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High doses of tigecycline are associated with satisfactory plasmatic and pulmonary concentrations for the treatment of severe infections due to fully susceptible bacteria: do we need even higher doses in patients under CRRT?高剂量替加环素对于治疗由完全敏感细菌引起的严重感染可达到令人满意的血浆和肺部浓度:对于接受连续性肾脏替代治疗(CRRT)的患者,我们是否需要更高的剂量?
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Cutaneous Hyperpigmentation Secondary to High-Dose Tigecycline: A Case Report.大剂量替加环素继发皮肤色素沉着:1例报告
Ther Adv Infect Dis. 2020 Aug 26;7:2049936120952605. doi: 10.1177/2049936120952605. eCollection 2020 Jan-Dec.
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