Topiramate concentrations in neonates treated with prolonged whole body hypothermia for hypoxic ischemic encephalopathy
Topiramate concentrations in neonates treated with prolonged whole body hypothermia for hypoxic ischemic encephalopathy
复制标题
DOI：
10.1111/j.1528-1167.2009.02302.x
复制
发表时间：
2009-11-01
期刊：
影响因子：
5.6
通讯作者：
Guerrini, Renzo
中科院分区：
文献类型：
--
作者：
Filippi, Luca;la Marca, Giancarlo;Guerrini, Renzo
目的：低温治疗可降低缺氧缺血性脑病新生儿的死亡率和神经功能障碍。托吡酯在窒息的新生动物模型中发挥神经保护作用。然而，没有研究调查低温和托吡酯的关联，因为低温期间托吡酯的药代动力学和最佳给药方案尚不清楚。以长期全身低温和托吡酯治疗的窒息新生儿为研究对象，评价低温对托吡酯药代动力学的影响。方法：对13名足月新生儿进行轻度或深度全身低温治疗72小时。所有患者在出生后的前 3 天均接受口服托吡酯治疗，剂量为 5 毫克/公斤，每天一次，其中 7 名患者同时接受苯巴比妥治疗。在连续的干血点上测量托吡酯浓度。结果：13 名新生儿中有 11 名托吡酯浓度在参考范围内，而 13 名新生儿中有 2 名托吡酯浓度超过上限，这两名新生儿均处于深低温状态。托吡酯浓度在九名新生儿中达到了虚拟稳态，并计算了其药代动力学参数。托吡酯最大和最小浓度、半衰期、平均浓度和时间-浓度曲线下面积的值比正常体温婴儿报告的值要高得多。对于常温婴儿，最大浓度时间略有延迟，表观全身清除率较低，表明吸收和消除较慢。深低温与轻度低温的婴儿之间以及托吡酯单药治疗与添加苯巴比妥的婴儿之间的药代动力学参数没有显着差异。 结论：大多数接受托吡酯 5 mg/kg 每天一次长期低温治疗的新生儿在整个治疗期间的药物浓度在参考范围内。
Purpose: Therapeutic hypothermia reduces mortality and neurologic impairment in neonates with hypoxic-ischemic encephalopathy. Topiramate exerts a neuroprotective effect in asphyxiated neonatal animal models. However, no studies have investigated the association of hypothermia and topiramate, because topiramate pharmacokinetics during hypothermia and the optimal administration schedule are unknown. The influence of hypothermia on topiramate pharmacokinetics was evaluated in asphyxiated neonates treated with prolonged whole-body hypothermia and topiramate.Methods: Thirteen term newborns were treated with mild or deep whole body hypothermia for 72 h; all received oral topiramate, 5 mg/kg once a day for the first 3 days of life, and seven had concomitant phenobarbital treatment. Topiramate concentrations were measured on serial dried blood spots.Results: Topiramate concentrations were within the reference range in 11 of 13 newborns, whereas concentrations exceeded the upper limit in 2 of 13, both newborns on deep hypothermia. Topiramate concentrations reached a virtual steady state in nine newborns, for whom pharmacokinetic parameters were calculated. Values of topiramate maximal and minimal concentration, half-life, average concentration, and area under the time-concentration curve resulted in considerably higher values than those reported in normothermic infants. With respect to normothermic infants, time of maximal concentration was mildly delayed and apparent total body clearance was lower, suggesting slower absorption and elimination. Pharmacokinetic parameters did not differ significantly between infants on deep versus mild hypothermia and in those on topiramate monotherapy versus add-on phenobarbital.Conclusion: Most neonates on prolonged hypothermia treated with topiramate 5 mg/kg once a day exhibited drug concentrations within the reference range for the entire treatment duration.