利福平影响伏立康唑血药浓度2例并文献复习

Effect of rifampicin on voriconazole concentration in plasma:a report of 2 cases and literature review

目的了解联合应用及停用利福平后对伏立康唑血药浓度的影响。方法对泉州第一医院2例利福平、异烟肼等抗结核药与伏立康唑联合应用或停用利福平后患者的伏立康唑血药浓度变化进行分析;并以"伏立康唑""利福平"为主题词检索万方、维普和中国知网数据库,以"voriconazole""rifampicin"为主题词检索PubMed数据库,对检索利福平影响伏立康唑血药浓度的患者资料进行筛选分析。结果1例在利福平、异烟肼等抗结核药与伏立康唑联合应用时监测伏立康唑谷浓度为0.2 mg/L,停用利福平后第7天伏立康唑谷浓度上升到1.0 mg/L;另1例停用利福平后开始使用伏立康唑,第4天伏立康唑的谷浓度为0,第7天上升到1.3 mg/L,第14天进一步上升到3.0 mg/L。文献检索到7例,利福平、异烟肼等抗结核药与伏立康唑联合应用3 d及以上,伏立康唑谷浓度均低于有效范围下限(1.0 mg/L);停用利福平8~10 d,伏立康唑谷浓度可恢复到有效治疗浓度范围(1.0~5.5 mg/L)。结论利福平是强效CYP450诱导剂,停药后仍可影响伏立康唑血药浓度。对于需要同时应用伏立康唑和利福平的患者,可考虑选用利福布汀替代利福平,在治疗药物监测下,进行剂量调整。

Objective To investigate the effect of administration and discontinuation of rifampicin on the plasma concentration of voriconazole.Methods The dynamic change of voriconazole plasma concentration was investigated in 2 patients who used rifampicin,isoniazid,and other anti-tuberculosis drugs in combination with voriconazole or started to use voriconazole after stopping rifampicin.Wanfang,VIP,CNKI and PubMed databases were searched with"voriconazole"and"rifampicin"as the search terms to retrieve the case reports about rifampicin effect on blood concentration of voriconazole.The reported cases were reviewed and summarized carefully.Results The trough plasma concentration of voriconazole was 0.2 mg/L in one case when rifampicin,isoniazid and other anti-tuberculosis drugs were combined with voriconazole.The trough plasma concentration of voriconazole increased from 0.2 mg/L to 1.0 mg/L 7 days after discontinuation of rifampicin in the patient.For the other patient,the trough plasma concentration of voriconazole was 0 on day 4,increased to 1.3 mg/L on day 7,and further increased to 3.0 mg/L on day 14 after discontinuation of rifampicin.Literature search identified 7 similar cases.When rifampicin,isoniazid,and other anti-tuberculosis drugs were combined with voriconazole for 3 days or more,the trough plasma concentration of voriconazole was lower than the lower limit of effective range(1.0 mg/L).The trough concentration of voriconazole returned to effective therapeutic concentration range(1.0-5.5 mg/L)8-10 days after discontinuation of rifampicin.Conclusions Rifampicin is a potent inducer of cytochrome P450 oxidative enzymes,which can affect the plasma concentration of voriconazole even after withdrawal.For patients who need to use voriconazole and rifampicin simultaneously,rifabutin can be considered to replace rifampicin.The dosage can be adjusted under the therapeutic drug monitoring.