伏立康唑与利福平药物相互作用的临床回顾性研究

Retrospective study on the interaction between voriconazole and rifampin in clinical patients

目的回顾性研究利福平对伏立康唑谷浓度的影响和影响持续的时间,以及两者相互作用的影响因素。方法收集2018年5月—2022年12月我院收治的均使用过伏立康唑和利福平且进行伏立康唑TDM的病例,汇总患者的一般资料、利福平给药方案、伏立康唑给药方案、其他合并用药及伏立康唑TDM结果。结果共纳入32例患者,15例同期联用利福平,17例未同期联用利福平。联用利福平组伏立康唑平均谷浓度为(1.58±3.01)mg/L,66.7%(10例)患者低于目标范围下限,达标率为26.7%;未联用利福平组伏立康唑平均谷浓度为(3.67±2.44)mg/L,0例患者谷浓度低于下限,达标率为82.4%,两组谷浓度分布存在显著统计学差异(P<0.01)。联用组中,谷浓度低于目标范围的10例患者,首次TDM时机均为停用利福平7 d内,其中6例患者停用利福平后多次复查谷浓度,3例在停药7 d后谷浓度上升至目标范围下限;联用组内首次TDM谷浓度>1.0 mg/L的5例患者中,3例为危重症患者,SOFA评分均大于10分,其中1例同时联用大剂量PPI;1例在利福平停药第7 d实施伏立康唑TDM;1例在联用利福平前谷浓度超标。结论伏立康唑与利福平联用时,谷浓度显著降低,利福平停药7 d以上,谷浓度可能恢复至目标范围内;利福平对伏立康唑的代谢诱导作用可能受患者病情严重程度的影响。

Objective To retrospectively study the induction and duration of rifampin on voriconazole trough concentration and the interfering factors of the interaction between rifampin and voriconazole.Methods The data of patients in our hospital who had been treated with voriconazole and rifampin and also underwent voriconazole TDM from May 2018 to December 2022 was collected.The basic information,rifampin regimen,voriconazole regimen,other co-medications and voriconazole TDM results were analyzed.Results A total of 32 patients were collected;15 patients had concomitant use of voriconazole with rifampin in the same period,while 17 patients did not.The mean trough concentration of voriconazole was(1.58±3.01)mg/L in the combined group,with 66.7%(10/15)of patients below the target range and 26.7%(4/15)of patients in the target range.The mean trough concentration was(3.67±2.44)mg/L in the uncombined group,with 82.4%(14/17)of patients achieving the target concentration and no patient below the target range.The distribution of voriconazole trough concentration between the two groups was significantly different(P<0.01).In the combined group,the initial TDM of 10 patients who were below the target range were all sampled within 7 days after discontinuing rifampin;6 patients repeated voriconazole TDM several times,while 3 patients achieved the therapeutic concentration after discontinuing rifampin for more than 7 days.There were 5 patients with voriconazole trough concentrations beyond 1.0 mg/L in the combined group,including 3 critically ill patients with a SOFA score greater than 10 and one patient who had coadministration with a heavy dose of PPI at the same time;one patient underwent TDM after discontinuing rifampin for 7 days;and one patient who had voriconazole trough concentrations over the target range twice before coadministration with rifampin.Conclusion The trough concentration of voriconazole will be significantly reduced when coadministration with rifampin,but may increase into the target range after discontinuing rifampin for more than 7 days.The induction of rifampin in voriconazole's metabolism may affected by the SOFA score of patients.