AUTHOR=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 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1118788

DOI=10.3389/fphar.2023.1118788

ISSN=1663-9812

ABSTRACT=<p><bold>Objective:</bold> 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.</p><p><bold>Methods:</bold> 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 (<italic>n</italic> = 6) or non-CRRT group (<italic>n</italic> = 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 <italic>t</italic>-test. Furthermore, between-groups comparisons adjusted for baseline value was also done using multivariate linear regression model.</p><p><bold>Results:</bold> Peak concentration (C<sub>max</sub>) of tigecycline was increased in CRRT group compared to non-CRRT group, but there were no statistical differences (505.11 ± 143.84 vs<italic>.</italic> 406.29 ± 108.00 ng/mL, <italic>p</italic>-value: 0.129). Trough concentration (C<sub>min</sub>) of tigecycline was significantly higher in CRRT group than in non-CRRT group, with statistical differences (287.92 ± 41.91 vs<italic>.</italic> 174.79 ± 33.15 ng/mL, <italic>p</italic>-value: 0.000, adjusted <italic>p</italic>-value: 0.000). In safety, C<sub>min</sub> was reported to be a useful predictor of hepatotoxicity with a cut-off of 474.8 ng/mL. In our studies, C<sub>min</sub> of all patients in CRRT group was lower than 474.8 ng/mL.</p><p><bold>Conclusion:</bold> The plasma concentration of tigecycline was increased in septic shock patients with CRRT treatment and only C<sub>min</sub> shown statistical differences. No dose adjustment seems needed in the view of hepatotoxicity.</p><p><bold>Clinical Trial Registration:</bold><ext-link ext-link-type="uri" xlink:href="https://www.chictr.org.cn/" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.chictr.org.cn/</ext-link>, identifier ChiCTR2000037475.</p>