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(,Voriconazolen,、,Liver Cirrhosis,、,severe liver dysfunction,),检索时间:,2005-201,7年,检索结果,:中文文献(,38,篇)、英文文献(,24,篇),文献筛选原则,:研究内容的有效性、文献类型(系统评,价或,meta,分析、,RCT,、综述等)、新颖度、质量等,文献筛选结果,:,4,篇,Altered Pharmacokinetics of Voriconazolen a Patient with Liver Cirrhosis,A 45-year-old male(,body weight,100 kg,),Fatty-liver cirrhosis(,Child-Pugh class C,;model of end-stage liver disease score,20)who was listed for liver transplantation and showed signs of,portal hypertension,(esophageal varices and ascites)and cholestasis(plasma bilirubin level,20.26 mg/dl,or 346 mol/liter),Received,2 mg of VRC/kg,of body weight orally,twice a day,because of suspected pulmonary aspergillosis.,At,day 30,of clinical treatment with VRC,he was transferred to the ICU because of unconsciousness(Glasgow Coma Scale score,5 of 15)and hyperventilation.,文献,1,:,肝硬化患者使用伏立康唑的药代动力学变化,半衰期:4.7h,53.1h,清除率:253.9 1.4mg/h/kg,文献,1,:,肝硬化患者使用伏立康唑的药代动力学变化,伏立康唑,80%,经肾脏排泄,,20%,经胆汁消除。,高浓度的伏立康唑呈现非线性动力学,半衰期延长。,conclusions,:,In patients with,moderate liver cirrhosis(Child-Pugh class B),a,reduction of the maintenance dose by,50%,is recommended for patients with mild to moderate hepatic insufficiency,.,For patients with,severely impaired liver function,a dose reduction of more than 50%,appears to be required,and,therapeutic drug monitoring,will greatly improve therapeutic safety.,对于重度肝功能损伤的患者,伏立康唑维持剂量减少,超过50%是必须的,应该进行治疗药物检测。,文献,1,:,肝硬化患者使用伏立康唑的药代动力学变化,Between 1999 and 2009,we screened all adult patients,admitted to the Liver Intensive Therapy Unit(LITU)at,Kings College Hospital in London and identified patients,who had a Model for End Stage Liver Disease(MELD),greater than 9 and had received at least 4 doses of voriconazole.,文献,2,:,伏立康唑在严重肝功能障碍患者的肝毒性,文献,2,:,伏立康唑在严重肝功能障碍患者的肝毒性,给予负荷剂量的患者有,13,人(,44.8%,),其余,16,人直接给予治疗剂量。,平均负荷剂量:,30245.9mg/day or 4.60.7mg/kg/day(200-400mg/day;3.3-5.5mg/kg/day),治疗剂量:,218.641.4mg/day or 3.630.7mg/kg/day(160-300mg/day;2.58-4.33mg/kg/day),给药次数:,25,人为,Qd,,,4,人为,Bid,平均治疗天数:,39.751.7days,(,5-180days,),文献,2,:,伏立康唑在严重肝功能障碍患者的肝毒性,文献,2,:,伏立康唑在严重肝功能障碍患者的肝毒性,69%,of patients treated with voriconazole showed changes in liver functiontests(LFTs)during therapy.The control group developed alterations in the LFTs in only,10.3%,of patients.,They showed elevated transaminases in,35%,cholestasis in,15%,or a combination of both in,45%,.According to the CTC classification,all patients with hepatotoxicity had a severe reaction.,There was,a correlation between initial loading dose greater than 300 mg(4.5 mg/kg)and the risk of hepatotoxicity,(p 0.001).,Voriconazole hepatotoxicity in severe liver Dysfunction.Journal of Infection(2013)66,80-86,文献,2,:,伏立康唑在严重肝功能障碍患者的肝毒性,文献,3,伏立康唑联合卡泊芬净成功治疗2例肝功能衰竭,合并侵袭性肺曲霉菌病,说明卡泊芬净与伏立康唑联用有一定的协同作用,Li D,,,Chert L,,,Ding X,,,et a1,Hospital,acquired invasive pulmonary aspergillosis in patients with hepatic failureJ,BMC Gastroenterol,,,2008,,,31,:,32,本研究中,2,例患者均采用了伏立康唑,+,卡泊芬净静脉应用和两性霉素,B,脂质体雾化吸入的三联抗曲霉菌治疗,未出现因药物因素导致的肝功能和,(,或,),肾功能进一步加重的表现,耐受性较好,并于联合用药后感染得到控制并逐渐好转。,2007年病例,酒精性肝硬化患者(child c)给予剂量为,负荷剂量4
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