Linezolid therapeutic drug monitoring in patients with hepatic impairment

Objective To investigate the distribution profile of trough plasma concentration (C_min) of linezolid in patients with hepatic impairment and the factors affecting concentration variation, and to evaluate treatment efficacy and linezolid-induced thrombocytopenia. Methods Hepatic impairment patients who received standard dose of linezolid (600 mg, q12 h) were stratified according to baseline hepatic function as defined by Child-Pugh-Turcotte score criteria: mild hepatic impairment (Child-Pugh-Turcotte Class A), moderate hepatic impairment (Child-Pugh-Turcotte Class B) and severe hepatic impairment (Child-Pugh-Turcotte Class C). Linezolid C_min was measured by high-performance liquid chromatography. Data pertaining to linezolid were collected. Multivariate linear regression models were used to investigate the effect of variables on linezolid C_min. Bacterial eradication rate and incidence of linezolid-induced thrombocytopenia were analyzed in terms of hepatic impairment. Results Plasma samples were collected from 30 patients. Severe hepatic impairment patients showed significantly higher linezolid C_min than the patients with mild or moderate hepatic impairment [(19.3 ± 6.5) mg/L vs (7.5 ± 3.2) mg/L, P < 0.05; (19.3 ± 6.5) mg/L vs (11.6 ± 3.2) mg/L, P < 0.05]. Supratherapeutic linezolid Cmin was observed in 11.8%, 42.1%, and 66.7% of the patients with mild, moderate, or severe hepatic impairment, respectively. Age(≥65 years), Charlson comorbidity score(≥4 points), and severe hepatic impairment had a significant effect on linezolid C_min (P < 0.05). Bacterial eradication rate and the incidence of linezolid-induced thrombocytopenia was 70.0% and 30.0% respectively in patients with hepatic impairment. Conclusions Standard dosing regimen of linezolid still achieves high plasma concentration in patients with hepatic impairment. Plasma concentrations of linezolid should be closely monitored in patients with hepatic impairment to ensure the safety and efficacy of linezolid therapy.