Department of Pharmacy, Mie University Hospital, Tsu, Mie, Japan.
Department of Clinical Pharmaceutics, Division of Clinical Medical Science, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Br J Clin Pharmacol. 2024 May;90(5):1222-1230. doi: 10.1111/bcp.16004. Epub 2024 Feb 6.
Although therapeutic drug monitoring (TDM) of voriconazole is performed in outpatients to prevent treatment failure and toxicity, whether TDM should be performed in all or only selected patients remains controversial. This study evaluated the association between voriconazole trough concentrations and clinical events.
We investigated the aggravation of clinical symptoms, incidence of hepatotoxicity and visual disturbances, change in co-medications and interaction between voriconazole and co-medications in outpatients receiving voriconazole between 2017 and 2021 in three facilities. Abnormal trough concentrations were defined as <1.0 mg/L (low group) and >4.0 mg/L (high group).
A total of 141 outpatients (578 concentration measurements) met the inclusion criteria (treatment, 37 patients, 131 values; prophylaxis, 104 patients, 447 values). The percentages of patients with abnormal concentrations were 29.0% and 31.5% in the treatment and prophylaxis groups, respectively. Abnormal concentrations showed 50% of the concentrations at the first measurement in both therapies. Aggravation of clinical symptoms was most frequently observed in the low treatment group (18.2%). Adverse events were most common in the high group for both therapies (treatment, hepatotoxicity 6.3%, visual disturbance 18.8%; prophylaxis, hepatotoxicity 27.9%). No differences were found in changes to co-medications and drug interactions. In the prophylaxis group, prescription duration in the presence of clinical events tended to be longer than in their absence (47.4 ± 23.4 days vs 39.7 ± 21.9 days, P = .1132).
We developed an algorithm based on clinical events for appropriate implementation of TDM in outpatients. However, future interventions based on this algorithm should be validated.
虽然治疗药物监测（TDM）在门诊中用于预防治疗失败和毒性，但 TDM 是否应在所有患者或仅在选定患者中进行仍存在争议。本研究评估了伏立康唑谷浓度与临床事件之间的关系。
我们调查了 2017 年至 2021 年在三个机构接受伏立康唑治疗的门诊患者中临床症状恶化、肝毒性和视觉障碍发生率、合并用药变化以及伏立康唑与合并用药相互作用的情况。异常谷浓度定义为 <1.0 mg/L（低浓度组）和 >4.0 mg/L（高浓度组）。
共有 141 名门诊患者（578 次浓度测量）符合纳入标准（治疗组 37 例，131 个值；预防组 104 例，447 个值）。治疗组和预防组异常浓度的患者比例分别为 29.0%和 31.5%。两种治疗方法的首次测量中，异常浓度分别占 50%。低治疗组临床症状恶化最常见（18.2%）。两种治疗方法中，高浓度组的不良事件最常见（治疗组：肝毒性 6.3%，视觉障碍 18.8%；预防组：肝毒性 27.9%）。合并用药和药物相互作用的变化无差异。在预防组中，有临床事件时的处方持续时间往往长于无临床事件时（47.4 ± 23.4 天 vs 39.7 ± 21.9 天，P =.1132）。
我们根据临床事件制定了一个适合门诊 TDM 实施的算法。然而，未来基于该算法的干预措施需要验证。
