Department of Internal Medicine, Seoul National University College of Medicine, Republic of Korea.
Clin Infect Dis. 2012 Oct;55(8):1080-7. doi: 10.1093/cid/cis599. Epub 2012 Jul 3.
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.
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.
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).
Routine TDM of voriconazole may reduce drug discontinuation due to adverse events and improve the treatment response in invasive fungal infections.
NCT00890708.
伏立康唑是侵袭性曲霉病的一线治疗药物，其血药浓度可能与不良事件和治疗反应相关。然而，目前尚无随机对照研究评估伏立康唑常规治疗药物监测（TDM）的临床实用性。本研究旨在确定伏立康唑常规 TDM 是否可减少药物不良事件或改善侵袭性真菌感染的治疗反应。
这是一项随机、评估者设盲、对照、单中心试验。110 例成年患者被随机分配至 TDM 或非 TDM 组。在 TDM 组中，根据伏立康唑起始后第 4 天的血清谷浓度调整伏立康唑剂量（目标范围：1.0-5.5 mg/L）。非 TDM 组接受固定、标准剂量。监测伏立康唑相关不良事件，并在治疗开始后 3 个月评估治疗反应。
两组患者的基线特征（包括 CYP2C19 基因型）相当。TDM 组和非 TDM 组的不良事件发生率无差异（均为 42%；P =.97），但 TDM 组因不良事件而停用伏立康唑的比例明显低于非 TDM 组（4% vs 17%；P =.02）。TDM 组中 81%（30/37）的患者获得完全或部分缓解，而非 TDM 组中这一比例为 57%（20/34）（P =.04）。
伏立康唑常规 TDM 可能减少因不良事件而停药，并改善侵袭性真菌感染的治疗反应。
NCT00890708。
