The Effect of Therapeutic Drug Monitoring on Safety and Efficacy of Voriconazole in Invasive Fungal Infections: A Randomized Controlled Trial
The Effect of Therapeutic Drug Monitoring on Safety and Efficacy of Voriconazole in Invasive Fungal Infections: A Randomized Controlled Trial
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DOI：
10.1093/cid/cis599
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发表时间：
2012-10-15
影响因子：
11.8
通讯作者：
Yu, Kyung-Sang
中科院分区：
文献类型：
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作者：
Park, Wan Beom;Kim, Nak-Hyun;Yu, Kyung-Sang
背景。伏立康唑是侵袭性曲霉病的一线治疗药物，其血液浓度可能与不良事件和治疗反应相关。然而，尚未进行随机对照研究来评估伏立康唑常规治疗药物监测（TDM）的临床效用。本研究旨在确定伏立康唑的常规 TDM 是否可以减少药物不良事件或改善侵袭性真菌感染的治疗反应。方法。这是一项随机、评估者盲法、对照、单中心试验。 110 名成年患者被随机分配到 TDM 组或非 TDM 组。 TDM组根据伏立康唑治疗后第4天测得的血清谷值调整伏立康唑剂量（目标范围1.0~5.5 mg/L）。非 TDM 组接受固定的标准剂量。监测伏立康唑相关的不良事件，并在治疗开始三个月后评估治疗反应。结果。两组之间的基线特征（包括 CYP2C19 基因型）具有可比性。虽然 TDM 组和非 TDM 组的不良事件发生率没有差异（均为 42%；P = .97），但 TDM 组因不良事件而停用伏立康唑的比例显着低于非 TDM 组（4% vs 17%；P = .02）。 TDM 组中有 81%（37 人中的 30 人）的患者出现完全或部分缓解，而非 TDM 组中这一比例为 57%（34 人中的 20 人）（P = 0.04）。结论。伏立康唑的常规 TDM 可以减少因不良事件而停药的情况，并改善侵袭性真菌感染的治疗反应。
Background. Blood levels of voriconazole, a first line therapy for invasive aspergillosis, may correlate with adverse events and treatment response. However, no randomized controlled studies have been conducted to evaluate the clinical utility of routine therapeutic drug monitoring (TDM) of voriconazole. This study aimed to determine whether routine TDM of voriconazole reduces drug adverse events or improves treatment response in invasive fungal infections.Methods. This was a randomized, assessor-blinded, controlled, single center trial. One hundred ten adult patients were randomly assigned to TDM or non-TDM groups. In the TDM group, voriconazole dosage was adjusted (target range, 1.0-5.5 mg/L) according to the serum trough level measured on the fourth day after initiation of voriconazole. The non-TDM group received a fixed, standard dosage. Voriconazole-related adverse events were monitored, and treatment response was assessed three months after the initiation of therapy.Results. Baseline characteristics including the CYP2C19 genotype were comparable between the two groups. While the incidence of adverse events was not different between the TDM group and the non-TDM group (both 42%; P = .97), the proportion of voriconazole discontinuation due to adverse events was significantly lower in the TDM group than in the non-TDM group (4% vs 17%; P = .02). A complete or partial response was observed in 81% (30 of 37) of patients in the TDM group compared to 57% (20 of 34) in the non-TDM group (P = .04).Conclusions. Routine TDM of voriconazole may reduce drug discontinuation due to adverse events and improve the treatment response in invasive fungal infections.