University College London, Division of Infection and Immunity, Royal Free Hospital, Rowland Hill Street, London NW3 2PF, UK.
Int J Antimicrob Agents. 2011 May;37(5):445-8. doi: 10.1016/j.ijantimicag.2010.11.033.
Ganciclovir (GCV) is used to treat babies and older children with cytomegalovirus-related disease. Treatment courses are generally derived from adult studies and there are few data relating to the pharmacokinetics of GCV in children. In adults, low trough GCV levels have been associated with treatment failure and virological resistance. Data regarding suitable drug levels for use in therapeutic drug monitoring (TDM) in the paediatric age group do not currently exist. In this study, anonymised data for all GCV levels sent to the UK Antibiotic Reference Laboratory from 1 November 1999 to 31 March 2007 were reviewed and analysed by age group. In total, 339 specimens were received from 129 patients; 192 specimens were from patients aged <18 years. There were significantly more trough GCV levels <0.5 mg/L in those aged <6 months and 6-12 months compared with adults (64.8% and 53.9%, respectively, vs. 15.9%; P<0.001). Those aged 5-18 years also had significantly more trough samples with levels <0.5 mg/L (80.0% vs. 15.9%; P<0.001). There was a significant difference between median peak GCV levels in those aged <6 months and adults (4.8 mg/L vs. 5.7 mg/L, respectively; P=0.047). In conclusion, GCV levels associated with treatment failure and considered subtherapeutic in adult patients were observed more often in specimens from paediatric patients. These lower levels may have implications for dosing in the paediatric age group, particularly during periods of rapid change in renal function such as the neonatal period. Clinicians should be aware of the relatively low drug exposure noted in this study and consider TDM and increasing drug dose where virological response is poor.
更昔洛韦（GCV）用于治疗巨细胞病毒相关疾病的婴儿和大龄儿童。治疗方案通常来源于成人研究，有关儿童更昔洛韦药代动力学的数据很少。在成人中，低谷浓度的 GCV 水平与治疗失败和病毒学耐药性相关。目前，尚无关于适合儿科年龄组治疗药物监测（TDM）使用的合适药物水平的数据。在这项研究中，对 1999 年 11 月 1 日至 2007 年 3 月 31 日期间从英国抗生素参考实验室发送的所有 GCV 水平的匿名数据进行了审查和按年龄组分析。共收到 129 名患者的 339 份标本；192 份标本来自年龄<18 岁的患者。年龄<6 个月和 6-12 个月的患者谷浓度 GCV 水平<0.5mg/L 的比例明显高于成人（分别为 64.8%和 53.9%，而成人的比例为 15.9%；P<0.001）。5-18 岁的患者谷浓度 GCV 水平<0.5mg/L 的样本也明显较多（80.0%比 15.9%；P<0.001）。年龄<6 个月的患者与成人的 GCV 峰浓度中位数有显著差异（分别为 4.8mg/L 和 5.7mg/L；P=0.047）。总之，在儿科患者的标本中，观察到与治疗失败相关且在成人患者中被认为是治疗不足的 GCV 水平更为常见。这些较低的水平可能会对儿科年龄组的剂量产生影响，尤其是在肾功能快速变化的时期，如新生儿期。临床医生应注意到本研究中观察到的相对较低的药物暴露，并考虑在病毒学反应不佳时进行 TDM 和增加药物剂量。
