Department of Pharmacy, the Second Xiangya Hospital, Central South University, Changsha, China.
Institute of Clinical Pharmacy, Central South University, Changsha, China.
Basic Clin Pharmacol Toxicol. 2019 Jul;125(1):34-43. doi: 10.1111/bcpt.13208. Epub 2019 Feb 27.
Voriconazole is a broad-spectrum antifungal agent commonly used to treat invasive fungal infections. Voriconazole has significant intraindividual and interindividual pharmacokinetics variability in different patient populations. Pharmacokinetic data of voriconazole in patients with liver dysfunction were limited. The aims of this study were to evaluate the population pharmacokinetics of voriconazole in patients with liver dysfunction and to identify the factors that affect voriconazole pharmacokinetics. A total of 166 samples taken from 57 patients with liver dysfunction were included in the study. A one-compartment pharmacokinetic model with first-order absorption and elimination was used to describe the data. Voriconazole clearance (CL) was 0.58 L/h, the volume of distribution (V ) was 134 L, and oral bioavailability (F) was 80.8%. This study showed that platelet count was significantly associated with voriconazole pharmacokinetic parameters. CYP2C19 polymorphisms had no effect on voriconazole pharmacokinetic parameters. Voriconazole CL was significantly decreased in patients with liver dysfunction. This study provides useful pharmacokinetics information for patients with liver dysfunction while highlighting the value of therapeutic drug monitoring in adjusting doses.
伏立康唑是一种广谱抗真菌药物，常用于治疗侵袭性真菌感染。伏立康唑在不同患者人群中的个体内和个体间药代动力学变异很大。肝功能障碍患者伏立康唑的药代动力学数据有限。本研究旨在评估肝功能障碍患者伏立康唑的群体药代动力学，并确定影响伏立康唑药代动力学的因素。本研究共纳入 57 例肝功能障碍患者的 166 个样本。采用一室模型加一级吸收和消除来描述数据。伏立康唑清除率（CL）为 0.58 L/h，分布容积（V）为 134 L，口服生物利用度（F）为 80.8%。本研究表明，血小板计数与伏立康唑药代动力学参数显著相关。CYP2C19 多态性对伏立康唑药代动力学参数无影响。肝功能障碍患者的伏立康唑 CL 显著降低。本研究为肝功能障碍患者提供了有用的药代动力学信息，同时强调了治疗药物监测在调整剂量方面的价值。
