Department of Pediatrics, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Republic of Korea.
Pediatr Blood Cancer. 2013 Jan;60(1):82-7. doi: 10.1002/pbc.24262. Epub 2012 Aug 8.
Voriconazole is the drug of choice for invasive aspergillosis (IA) and drug levels are influenced by interactions with other drugs and genetic predisposition. We performed a retrospective analysis of voriconazole drug levels and investigated the adequacy of drug levels in pediatric cancer patients and hematopoietic cell transplant (HCT) recipients with IA.
Trough serum concentrations of voriconazole in patients younger than 19 years during a 30-month period were analyzed. The therapeutic range was determined as 1-6 µg/ml.
A total of 193 voriconazole measurements at steady-state [86 on intravenous (IV) and 107 on oral (PO) doses] were obtained from 27 patients (median age 12.2 years). On the first monitoring, 19 patients (70.4%) achieved the therapeutic range. However, only 10 patients (37.0%) achieved the therapeutic range on second monitoring. Sixty-four percent of the total measurements were within the therapeutic range: 66.3% of IV and 61.7% of PO. A significant correlation between oral doses and trough levels of voriconazole was observed in patients ≤6 years old (Spearman's rank correlation coefficient = 0.4819, P = 0.027). Patients aged ≤6 years needed a significantly higher median dose of PO voriconazole to maintain therapeutic trough levels compared to older patient groups (8.9 vs. 4.2 mg/kg/dose, P < 0.001). Voriconazole level <1 µg/ml was more frequently observed in patients with treatment failure at week 6 of voriconazole therapy (failure vs. success, 42.1% vs. 19.7%; P = 0.012).
Serum concentrations of voriconazole in children were variable, depending on the patient's age and route of administration. Continuous and careful drug level monitoring should be performed.
伏立康唑是治疗侵袭性曲霉病（IA）的首选药物，其药物水平受与其他药物相互作用和遗传易感性的影响。我们对伏立康唑药物水平进行了回顾性分析，并研究了患有 IA 的儿科癌症患者和造血细胞移植（HCT）受者的药物水平是否充足。
分析了 30 个月期间年龄小于 19 岁的患者的伏立康唑稳态时的血清浓度。治疗范围确定为 1-6 µg/ml。
从 27 名患者（中位年龄 12.2 岁）获得了 193 次伏立康唑稳态下的测量值（静脉注射[IV]86 次，口服[PO]107 次）。在第一次监测时，19 名患者（70.4%）达到了治疗范围。然而，只有 10 名患者（37.0%）在第二次监测时达到了治疗范围。总测量值的 64%在治疗范围内：IV 为 66.3%，PO 为 61.7%。在≤6 岁的患者中，观察到口服剂量与伏立康唑谷浓度之间存在显著相关性（Spearman 秩相关系数=0.4819，P=0.027）。与年龄较大的患者组相比，≤6 岁的患者需要更高的 PO 伏立康唑中位剂量来维持治疗性谷浓度（8.9 与 4.2mg/kg/剂量，P<0.001）。在伏立康唑治疗第 6 周治疗失败的患者中，更频繁地观察到伏立康唑水平<1µg/ml（失败与成功，42.1%与 19.7%；P=0.012）。
儿童伏立康唑的血清浓度因患者年龄和给药途径而异。应进行持续和仔细的药物水平监测。
