Zhang Qian, Gao Xing, Lv Dongmei
Xuzhou Medical University, Xuzhou, China.
Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Front Pharmacol. 2025 Mar 28;16:1510890. doi: 10.3389/fphar.2025.1510890. eCollection 2025.
This study aimed to investigate the impact of the gene polymorphism on the blood drug concentrations of voriconazole in patients with severe invasive fungal infections. A total of 101 patients treated with voriconazole were enrolled in this study. Polymerase chain reaction and Sanger sequencing were used to detect the genotype of , and enzyme amplified immunoassay was used to detect the plasma trough concentration of voriconazole. We analyzed the impacts of patient genotype and the minimum concentration of voriconazole as well as investigated the treatment efficacy and rates of adverse reactions in patients with different genotypes. All subjects received standard-dose voriconazole treatment for 1 week, and the mean plasma concentration was found to be 4.5 (3.10, 6.90) mg/L. Three genotypes of were found in the study cohort, namely, wild type (CC type), heterozygous mutant type (CT type), and homozygous mutant type (TT type). There were 18 TT, 48 CT, and 35 CC type cases. Patients with different genotype groups and varying plasma trough concentrations did not differ statistically significantly in terms of the treatment efficacy or incidence of adverse events. Voriconazole plasma concentrations differed significantly among patients of different genders and genotypes. By incorporating gender into the multiple regression model, the regression equations were obtained as C1 = 6.09-1.33×Gender (male = 0, female = 1)-0.47× X1 (X1: T/T = 1, non-T/T = 0) and C2 = 6.09-1.33×Gender (male = 0, female = 1)-0.94×X1 (X1: T/T = 1, non-T/T = 0). The genotype was not found to affect voriconazole plasma trough concentrations in patients with invasive fungal infections admitted to the intensive care unit.
本研究旨在探讨基因多态性对重症侵袭性真菌感染患者伏立康唑血药浓度的影响。本研究共纳入101例接受伏立康唑治疗的患者。采用聚合酶链反应和桑格测序法检测某基因的基因型，采用酶放大免疫测定法检测伏立康唑的血浆谷浓度。我们分析了患者基因型和伏立康唑最低浓度的影响，并调查了不同基因型患者的治疗效果和不良反应发生率。所有受试者接受标准剂量伏立康唑治疗1周，发现平均血浆浓度为4.5（3.10，6.90）mg/L。在研究队列中发现了该基因的三种基因型，即野生型（CC型）、杂合突变型（CT型）和纯合突变型（TT型）。有18例TT型、48例CT型和35例CC型病例。不同基因型组和血浆谷浓度不同的患者在治疗效果或不良事件发生率方面无统计学显著差异。不同性别和该基因不同基因型患者的伏立康唑血浆浓度存在显著差异。将性别纳入多元回归模型后，得到回归方程为C1 = 6.09 - 1.33×性别（男性 = 0，女性 = 1） - 0.47×X1（X1：T/T = 1，非T/T = 0）和C2 = 6.09 - 1.33×性别（男性 = 0，女性 = 1） - 0.94×X1（X1：T/T = 1，非T/T = 0）。在重症监护病房收治的侵袭性真菌感染患者中，未发现该基因的基因型影响伏立康唑的血浆谷浓度。
