肝功能不全患者伏立康唑血药浓度监测回顾性研究

Retrospective analysis of voriconazole in the monitoring of therapeutic drugs in patients with liver dysfunction

目的:分析伏立康唑在肝功能不全患者中治疗药物监测结果,评估其与给药方案和安全性的关系,为临床个体化用药提供参考。方法:通过检索建库至2019年12月PubMed、Cochrane Library、万方、维普、中国期刊全文数据库,伏立康唑在肝功能不全患者中血药浓度及安全性信息,分析肝功能不全患者伏立康唑给药方案及血药浓度安全范围。结果:根据纳入标准共筛选出文献10篇,5篇为多样本回顾性研究,1篇为前瞻性研究,其余4篇为案例报道。Child-Pugh C级肝功能不全患者,采用维持剂量100 mg每12 h一次(q12h)安全性较高。伏立康唑不良反应的发生时间一般在7 d之内,目标谷浓度小于5 mg/L或5.3 mg/L时,不良反应发生率仍较高。主要不良反应包括神经毒性、幻觉、视觉障碍、胃肠道反应、皮疹等。结论:肝功能不全患者伏立康唑给药剂量应减量,并及时监测血药浓度,建议在保证疗效基础上,可进一步降低谷浓度以减少不良反应的发生。

AIM:To evaluate relationship between dosing schedules and safety of voriconazole by analyzing the monitoring results of voriconazole in patients with liver dysfunction,and to provide reference for the clinical individualized medication.METHODS:The blood concentration and safety information of voriconazole in patients with liver dysfunction was searched in PubMed,Cochrane Library,Wanfang,Weipu,and Chinese Journal Full-text Database from the establishment of the databases to December 2019,the dosing schedule and safety range of voriconazole for patients with liver dysfunction was analyzed.RESULTS:A total of 10 literatures were selected,5 of which were multi-sample retrospective studies and 1 of which was prospective study,and the remaining 4 were case reports.In Child-Pugh grade C liver dysfunction,a maintenance dose of 100 mg q12 h is more secure.The incidence of adverse reactions of voriconazole is generally within 7 days.When the target trough concentration is less than 5 mg/L or 5.3 mg/L,the incidence of adverse reactions is still high.The main adverse reactions include neurotoxicity,hallucinations,visual disturbances,gastrointestinal reactions and rash.CONCLUSION:The dose of voriconazole in patients with liver dysfunction should be reduced,and the drug concentration should be monitored in a timely manner.It is recommended that on the basis of ensuring the efficacy,trough concentration can be further reduced to reduce the occurrence of adverse reactions in patients with liver dysfunction.