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.

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http://dx.doi.org/10.3389/fphar.2023.1118788DOI Listing

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