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
Department of Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
School of Pharmacy, Nanjing Medical University, Nanjing, China.
Front Pharmacol. 2023 Mar 9;14:1118788. doi: 10.3389/fphar.2023.1118788. eCollection 2023.
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.
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