利福平对伏立康唑血药浓度的影响能持续多久?

How long can the effect of rifampicin on the plasma concentration of voriconazole last?

1例56岁男性肺结核合并感染的患者在给予莫西沙星联合利福平、异烟肼、乙胺丁醇、吡嗪酰胺治疗后病情不见好转。经支气管肺泡灌洗液培养以及1,3⁃β⁃D⁃葡聚糖、半乳甘露聚糖抗原和曲霉菌抗体检测确诊为侵袭性肺曲霉菌病。停用莫西沙星和抗结核药物,给予伏立康唑静脉滴注(首日300 mg、1次/12 h,维持剂量150 mg、1次/12 h)。用药第5天检测伏立康唑血药浓度,结果为0。药师会诊认为血药浓度的结果与利福平的影响有关。次日将伏立康唑剂量调整为200 mg、1次/12 h。2 d后复查伏立康唑血药浓度为1.3 mg/L。患者咳嗽、咳痰症状缓解,但仍反复高热。伏立康唑加量第9天,经风湿科医师会诊考虑结缔组织病不能排除,给予甲泼尼龙40 mg静脉滴注、1次/d。次日患者体温恢复正常,伏立康唑血药浓度为3.0 mg/L。经临床药师与医师共同复习文献,达成共识:利福平对体内药物代谢酶的诱导作用在停用该药后可持续7~10 d甚至更长,对利福平序贯伏立康唑治疗的患者应加强伏立康唑血药浓度监测,根据血药浓度调整伏立康唑剂量,直至利福平对药物代谢酶诱导作用完全消退,伏立康唑血药浓度达到稳态。

A 56⁃year⁃old male patient with tuberculosis complicated by infection did not get better after treatment with moxifloxacin combined with rifampicin,isoniazid,ethambutol,and pyrazinamide.The invasive pulmonary aspergillosis was diagnosed by bronchoalveolar lavage fluid culture and detection of 1,3⁃beta⁃D⁃glucan,galactomannan antigen,and Aspergillus antibody.Moxifloxacin and anti⁃tuberculosis drugs were discontinued and an IV infusion of voriconazole(the dose was 300 mg once per 12 hours on the first day,the maintenance dose was 150 mg once per 12 hours)was given.On the 5th day of medication,the plasma concentration of voriconazole was zero.The consultation pharmacist considered that the voriconazole plasma concentration was related to rifampicin.The next day,the dose of voriconazole was adjusted to 200 mg once per 12 hours.Two days later,the plasma concentration of voriconazole was 1.3 mg/L.The patient′s cough and expectoration were relieved,but he still repeatedly developed high fever.On the 9th day of increase of voriconazole dose,intravenous infusion of methylprednisolone 40 mg once daily was given because connective tissue disease could not be excluded by consulting rheumatologists.The patient′s temperature returned to normal the next day and the plasma concentration of voriconazole was 3.0 mg/L.Clinical pharmacists and physicians reviewed the literature and reached a consensus:the induction effect of rifampicin on drug metabolizing enzymes in the body can last for 7⁃10 days or even longer after discontinua⁃tion of the drug,the monitoring of plasma concentration of voriconazole should be strengthened in patients treated with rifampicin sequential voriconazole,and the dose of voriconazole should be adjusted according to the plasma concentration until the induction effect of rifampicin on drug metabolizing enzymes completely disappears and the plasma concentration of voriconazole reaches a steady state.