Department of Pharmacy, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Department of Pharmacy, The First Hospital of Changsha, Changsha, Hunan, China.
Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0112624. doi: 10.1128/aac.01126-24. Epub 2024 Oct 21.
This study aims to describe the distribution characteristics of voriconazole (VRC) plasma trough concentrations () in patients with liver dysfunction, identify factors influencing VRC , and provide recommendations for the use of VRC in this population. We retrospectively collected medical records of hospitalized patients with liver dysfunction who used VRC and underwent therapeutic drug monitoring (TDM) at the First Hospital of Changsha. The severity of liver dysfunction was assessed by the Child-Pugh (CP) score. Multiple linear regression was employed to explore factors affecting VRC in these patients. A total of 147 from 102 patients with liver dysfunction were analyzed. Patients were categorized into a control group ( = 40), CP-A ( = 39), CP-B ( = 11), and CP-C group ( = 12). The initial probability of target attainment of was 70.6%, with 6.9% of patients obtaining subtherapeutic and 22.5% obtaining supertherapeutic . The initial in CP-A and B were 5.05 (0.64-9.57) mg/L and 5.37 (0.26-10.01) mg/L, respectively, significantly higher than the control group ( = 0.021 and = 0.010). The proportion of VRC of >5.5 mg/L in CP-A and B was 33.3% and 45.5%, respectively. Multiple linear regression analysis revealed that factors such as age ≥70 years, CP class, C-reactive protein (CRP), and direct bilirubin were significantly related to the initial VRC . Among all measurements, patients with severe inflammation (CRP >100 mg/L), aged ≥70 years, and albumin levels of <30 or <25 g/L had significantly higher VRC . The treatment success rate of VRC was 69.6% (71 of 102), and the rate of VRC-related adverse drug reactions was 29.4% (30 of 102). The recommended half-maintenance dose may lead to elevated VRC in patients with CP-A and CP-B. TDM is essential for patients with advanced age, severe infections, or hypoalbuminemia to prevent excessive VRC trough levels.
本研究旨在描述肝功能障碍患者伏立康唑（VRC）血药谷浓度（）的分布特征，确定影响 VRC 的因素，并为该人群使用 VRC 提供建议。我们回顾性收集了在长沙市第一医院住院的肝功能障碍患者的病历，这些患者使用了 VRC 并进行了治疗药物监测（TDM）。肝功能障碍的严重程度通过 Child-Pugh（CP）评分进行评估。采用多元线性回归分析探讨影响这些患者 VRC 的因素。共分析了 102 例肝功能障碍患者的 147 个 VRC。患者分为对照组（=40）、CP-A 组（=39）、CP-B 组（=11）和 CP-C 组（=12）。初始目标达标率为 70.6%，6.9%的患者获得治疗性 VRC，22.5%的患者获得超治疗性 VRC。CP-A 和 B 的初始 VRC 分别为 5.05（0.64-9.57）mg/L 和 5.37（0.26-10.01）mg/L，显著高于对照组（=0.021 和=0.010）。CP-A 和 B 的 VRC>5.5mg/L 的比例分别为 33.3%和 45.5%。多元线性回归分析显示，年龄≥70 岁、CP 分级、C 反应蛋白（CRP）和直接胆红素等因素与初始 VRC 显著相关。在所有测量中，炎症严重（CRP>100mg/L）、年龄≥70 岁和白蛋白水平<30 或<25g/L 的患者 VRC 显著升高。VRC 的治疗成功率为 69.6%（71/102），VRC 相关不良反应发生率为 29.4%（30/102）。推荐的半维持剂量可能导致 CP-A 和 CP-B 患者 VRC 升高。对于年龄较大、严重感染或低白蛋白血症的患者，TDM 是预防 VRC 谷浓度过高的关键。
