伏立康唑治疗多发性骨髓瘤患者侵袭性真菌感染的治疗药物监测

Therapeutic drug monitoring of voriconazole in multiple myeloma patients with invasive fungal disease

目的观察伏立康唑(VRZ)治疗多发性骨髓瘤(MM)患者侵袭性真菌感染(IFD)的有效性及安全性。方法所有患者均给予伏立康唑片每次200 mg,bid,口服或每次200 mg,q12 h,口服。在给药开始后4~7 d,用液相色谱-质谱联用法测定伏立康唑的血药浓度,并对药物不良反应(ADR)的发生高危因素进行单因素分析和多变量Logistics回归分析。结果纳入30次VRZ治疗(26例)的MM患者,血药浓度均值为(2.73±1.45)μmol·L^-1。VRZ治疗期间肝毒性发生率为40.0%,精神毒性发生率为20.0%,视觉异常发生率为6.7%。χ^2分析表明,细胞色素P4502C19(CYP2C19)基因型与VRZ浓度无相关性,VRZ浓度与任一ADR均无相关性。多元Logistic回归分析显示,患者的年龄越大,则肝毒性发生风险越高(P<0.05);对于精神毒性,给药前γ-谷氨酰转肽酶水平异常(P<0.05)和白蛋白水平低(P<0.05)则提示其发生高风险;未发现影响视觉毒性发生的因素。结论VRZ治疗MM患者IFD时,需密切监测其血药浓度与不良事件的发生。

Objective To determine the efficacy and safety of voriconazole(VRZ)in the treatment of invasive fungal infection(IFD)in patients with multiple myeloma(MM).Methods All patients were given VRZ tablets 200 mg,bid,orally or 200 mg,q12 h.The plasma concentration of VRZ was determined by liquid chromatography-mass spectrometry at 4-7 days after administration,and the risk factors of adverse drug reactions(ADR)were analyzed by univariate Logistic regression analysis.Results The mean plasma concentration of MM was(2.73±1.45)μmol·L^-1.During VRZ treatment,the incidences of hepatotoxicity,psychotoxicity and visual abnormality were 40.0%,20.0% and 6.7%,respectively.The results of chi-square analysis showed that there was no correlation between cytochrome P4502C19(CYP2C19)genotype and VRZ concentrations,nor was between VRZ concentrations and any ADR.Multivariate Logistic regression analysis showed that the older the patients were,the higher the risk of hepatotoxicity was(P<0.05);for psychotoxicity,the abnormal levels of gamma glutamyltranspeptidase(P<0.05)and low albumin level(P<0.05)before administration indicated higher risk;no factors affecting the occurrence of visual toxicity were found.Conclusion VRZ should be closely monitored the blood drug concentration and adverse events in the treatment of MM patients with IFD.