合并使用P糖蛋白抑制剂致利奈唑胺血药浓度超标的病例对照研究

Case-control Study of Excessive Linezolid Plasma Concentration Combined with P Glycoprotein Inhibitors

关键词:  浓度超标  血小板减少  相关性  P-gp抑制剂  危险因素

Key words:  concentration exceeding the standard  thrombocytopenia  correlation  P-gp inhibitors  risk factors

摘要:

目的 探索包括合并使用P糖蛋白(P glycoprotein，P-gp)抑制剂在内的各项因素对利奈唑胺血药浓度超标的影响，以降低因利奈唑胺高浓度导致的不良反应。方法 回顾性分析浙江大学医学院附属第一医院2018年1月—2019年12月使用利奈唑胺治疗并进行浓度检测的患者，研究利奈唑胺浓度超标与血小板减少不良反应的相关性，并对利奈唑胺浓度超标进行危险因素分析。结果 共纳入102例患者，发生血小板减少35例，该不良反应的发生与利奈唑胺的最高谷浓度成正相关(Kendall’s tau-b=0.418，P<0.001)。二元Logistic回归分析发现，肌酐清除率、使用剂数及联合P-gp抑制剂是利奈唑胺浓度超标(>8 mg·L^-1)的独立危险因素，联合P-gp抑制剂的OR值高达4.132(95%CI 1.250~13.657，P=0.020)。联合P-gp抑制剂与血小板减少的相关性尚无统计学意义。结论 利奈唑胺浓度超标与血小板减少有关，联合P-gp抑制剂是利奈唑胺浓度超标的重要危险因素，应关注利奈唑胺治疗时的合并用药，降低不良反应。

Abstract:

OBJECTIVE To explore the effects of various factors including the combined use of P-glycoprotein(P-gp) inhibitors on the concentration of linezolid exceeding the standard, so as to reduce the adverse reactions caused by the high concentration of linezolid. METHODS A retrospective analysis of patients treated with linezolid and concentration detected in the First Affiliated Hospital of Zhejiang University School of Medicine from January 2018 to December 2019 was conducted, to study the association of linezolid concentration exceeding the standard with adverse effects of thrombocytopenia and to perform a risk factor analysis for linezolid concentration exceeding the standard. RESULTS A total of 35 patients had thrombocytopenia in 102 cases treated with linezolid. The occurrence of this adverse reaction was positively correlated with the highest valley concentration of linezolid(Kendall’s tau-b=0.418, P<0.001). Binary logistic regression analysis found that creatinine clearance, number of doses used and combined with P-gp inhibitors were risk factors for linezolid concentrations exceeding the standard(>8 mg·L^-1), and OR of combination with P-gp inhibitors was 4.132(95%CI 1.250-13.657, P=0.020). The correlation between combined P-gp inhibitors and thrombocytopenia was not statistically significant. CONCLUSION The linezolid concentration exceeding the standard is related to thrombocytopenia, combination of P-gp inhibitors is an important risk factor for linezolid concentration exceeding the standard. In order to reduce the occurrence of adverse reactions, attention should be paid to the combined use of linezolid.