肝损伤患者利奈唑胺的治疗药物监测

Linezolid therapeutic drug monitoring in patients with hepatic impairment

目的探究肝损伤患者中利奈唑胺谷浓度(Cmin)的分布特征及影响浓度变化的因素,并对疗效及其诱导的血小板减少进行分析。方法根据Child-Pugh-Turcotte评分等级将使用利奈唑胺标准给药方案(600 mg,1次/12 h)的肝损伤患者分为轻度肝损伤组(Child-Pugh-Turcotte A级)、中度肝损伤组(Child-Pugh-Turcotte B级)和重度肝损伤组(Child-Pugh-Turcotte C级),采用高效液相法测定利奈唑胺的血药浓度。收集利奈唑胺用药相关信息,采用多元线性回归探讨影响利奈唑胺Cmin的因素。统计肝损伤患者中利奈唑胺血药浓度对细菌清除率及其致血小板减少的发生率。结果共监测30例肝损伤患者。重度肝损伤患者利奈唑胺Cmin显著高于轻、中度肝损伤患者[(19.3±6.5)mg/L对(7.5±3.2)mg/L,P<0.05;(19.3±6.5)mg/L对(11.6±3.2)mg/L,P<0.05]。轻度、中度和重度肝损伤组中分别有11.8%、42.1%和66.7%的Cmin高于治疗窗上限。多元线性回归分析结果表明利奈唑胺Cmin与患者年龄(≥65岁)、查尔森合并症评分(≥4分)和重度肝损伤具有显著相关性(P<0.05)。在肝损伤患者中利奈唑胺对细菌清除率为70.0%,诱导血小板减少发生率为30.0%。结论在肝损伤患者使用标准给药方案后利奈唑胺仍具有较高的血药浓度,特别是中度和重度肝损伤患者,并且相关血小板减少发生率高。年龄、查尔森合并症评分和重度肝损伤是利奈唑胺体内浓度的影响因素。肝损伤患者使用利奈唑胺应密切监测血药浓度,以保证临床治疗的安全性和有效性。

Objective To investigate the distribution profile of trough plasma concentration(Cmin)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 Cmin 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 Cmin.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 Cmin 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 Cmin(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.