Cabral-Galeano Evelyn, Ruiz-Camps Isabel, Len-Abad Oscar, Pou-Clavé Leonor, Sordé-Masip Roger, Meije-Castillo Yolanda, Blanco-Grau Albert, Barba-Suñol Pere, Monforte-Torres Victor, Román-Broto Antonio, Pahissa-Berga Albert, Gavaldà-Santapau Joan
Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Enferm Infecc Microbiol Clin. 2015 May;33(5):298-302. doi: 10.1016/j.eimc.2014.09.005. Epub 2014 Nov 4.
The aim of this study was to assess the clinical usefulness of therapeutic drug monitoring (TDM) of voriconazole (VOR) in a university hospital.
A retrospective review was conducted on the clinical records of 52 patients treated with VOR and on whom TDM was performed. Steady-state trough plasma VOR concentration was measured at least 5 days after starting treatment. The therapeutic range of plasma VOR concentration was defined as 1-5.5μg/mL.
The most frequent underlying conditions in the study population were lung transplant (48.1%) and hematological malignancies (26.9%). At the first TDM in each patient, VOR levels were outside the therapeutic range in 16 (30.7%) cases: <1μg/mL in 10 (19.2%) and >5.5μg/mL in 6 (11.5%). Eleven patients (21.2%) experienced severe muscle weakness and had considerable difficulty walking. All these patients were receiving concomitant treatment with corticosteroids. Age younger than 30 years (p=.005) and cystic fibrosis as the underlying disease (p=.04) were factors associated with low VOR levels. Almost all patients who had VOR concentrations >1μg/mL at the first TDM had a successful outcome (96%).
Plasma VOR concentrations were outside the therapeutic range at the first TDM in 30% (16/52) of patients. Age younger than 30 years and cystic fibrosis were factors associated with low VOR levels. The potential interactions between corticosteroids and VOR should be highlighted, as they could be responsible for a high rate of muscle weakness observed in our patients. Prospective trials are needed to investigate VOR TDM and corticosteroid pharmacokinetics.
本研究旨在评估伏立康唑（VOR）治疗药物监测（TDM）在一所大学医院中的临床实用性。
对52例接受VOR治疗并进行TDM的患者的临床记录进行回顾性分析。在开始治疗至少5天后测量稳态谷浓度血浆VOR浓度。血浆VOR浓度的治疗范围定义为1 - 5.5μg/mL。
研究人群中最常见的基础疾病是肺移植（48.1%）和血液系统恶性肿瘤（26.9%）。在每位患者的首次TDM时，16例（30.7%）患者的VOR水平超出治疗范围：10例（19.2%）<1μg/mL，6例（11.5%）>5.5μg/mL。11例患者（21.2%）出现严重肌无力且行走困难。所有这些患者均同时接受皮质类固醇治疗。年龄小于30岁（p = 0.005）和潜在疾病为囊性纤维化（p = 0.04）是与低VOR水平相关的因素。几乎所有在首次TDM时VOR浓度>1μg/mL的患者都取得了成功的治疗结果（96%）。
30%（16/52）的患者在首次TDM时血浆VOR浓度超出治疗范围。年龄小于30岁和囊性纤维化是与低VOR水平相关的因素。应强调皮质类固醇与VOR之间的潜在相互作用，因为它们可能是导致我们的患者中出现高比例肌无力的原因。需要进行前瞻性试验来研究VOR TDM和皮质类固醇的药代动力学。
