Department of Pharmacy, Tongji Hospital of Tongji Medical College, Huazhong University of Science & Technology, 13 Hangkong Road, Wuhan, Hubei 430030, China.
School of Pharmacy, Huazhong University of Science & Technology, Wuhan, China.
Int J Antimicrob Agents. 2017 Apr;49(4):483-487. doi: 10.1016/j.ijantimicag.2016.11.028. Epub 2017 Jan 31.
The pharmacokinetic profile of voriconazole is highly variable, rendering inconsistent and/or inadequate dosing, especially in children <2 years old. A retrospective analysis was performed in children receiving voriconazole with at least one plasma trough level (C) monitored. Statistical analyses were performed to examine the dose-exposure relationship as well as other factors potentially affecting voriconazole C in children of different ages. A total of 107 paediatric patients were included, of whom 75 were <2 years old. The voriconazole C was highly variable in patients aged <2 years and those aged 2-12 years. Only 47.7% of children reached the therapeutic target of 1.0-5.5 mg/L at initial dosing, whereas 48.6% of C values were subtherapeutic and 3.7% were supratherapeutic. The mean maintenance dose to reach an adequate C was 5.9 mg/kg compared with 5.1 mg/kg, resulting in insufficient levels (P = 0.005) in children aged <2 years. In this age group, the 5 to <7 mg/kg dose range significantly increased the chance of reaching the therapeutic target compared with the 3 to <5 mg/kg dose range (56.7% vs. 25.8%; P = 0.014). Overall, factors such as sex, age, liver function, renal function and co-administered medications explained only 15.9% of variability in voriconazole exposure. Co-administration of omeprazole significantly increased the voriconazole level (P = 0.032), likely through CYP2C19 inhibition. This is the largest series to date describing voriconazole dose-exposure relationships in children aged <2 years. A starting maintenance dose of 5 to <7 mg/kg intravenously twice daily may be required for most children of Asian origin to reach the therapeutic target.
伏立康唑的药代动力学特征高度可变，导致剂量不一致和/或不足，尤其是在<2 岁的儿童中。对接受伏立康唑治疗且至少监测了一个血药谷浓度（C）的儿童进行了回顾性分析。进行了统计学分析，以检查剂量-暴露关系以及其他可能影响不同年龄儿童伏立康唑 C 的因素。共纳入 107 例儿科患者，其中 75 例<2 岁。<2 岁和 2-12 岁的患者伏立康唑 C 高度可变。初始剂量时仅 47.7%的儿童达到 1.0-5.5mg/L 的治疗目标，而 48.6%的 C 值低于治疗范围，3.7%高于治疗范围。达到足够 C 的维持剂量平均为 5.9mg/kg，而 5.1mg/kg 则导致<2 岁儿童的 C 值不足（P=0.005）。在该年龄组中，与 3-<5mg/kg 剂量范围相比，5-<7mg/kg 剂量范围显著增加了达到治疗目标的机会（56.7% vs. 25.8%；P=0.014）。总体而言，性别、年龄、肝功能、肾功能和合并用药等因素仅解释了伏立康唑暴露变异性的 15.9%。奥美拉唑的合并使用显著增加了伏立康唑水平（P=0.032），可能是通过 CYP2C19 抑制作用。这是迄今为止描述<2 岁儿童伏立康唑剂量-暴露关系的最大系列研究。大多数亚洲裔儿童可能需要静脉注射每日两次 5-<7mg/kg 的起始维持剂量才能达到治疗目标。
