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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Amikacin Pharmacokinetics To Optimize Dosing in Neonates with Perinatal Asphyxia Treated with Hypothermia
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Amikacin Pharmacokinetics To Optimize Dosing in Neonates with Perinatal Asphyxia Treated with Hypothermia

机译：Amikacin药代动力学通过用体温过低治疗的围产期窒息优化给新生儿的剂量

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Aminoglycoside pharmacokinetics (PK) is expected to change in neonates with perinatal asphyxia treated with therapeutic hypothermia (PATH). Several amikacin dosing guidelines have been proposed for treating neonates with (suspected) septicemia; however, none provide adjustments for cases of PATH. Therefore, we aimed to quantify the differences in amikacin PK between neonates with and without PATH to propose suitable dosing recommendations. Based on amikacin therapeutic drug monitoring data collected retrospectively from neonates with PATH, combined with a published data set, we assessed the impact of PATH on amikacin PK by using population modeling. Monte Carlo and stochastic simulations were performed to establish amikacin exposures in neonates with PATH after dosing according to the current guidelines and according to proposed model-derived dosing guidelines. Amikacin clearance was decreased 40.6% in neonates with PATH, with no changes in volume of distribution. Simulations showed that increasing the dosing interval by 12 h results in a decrease in the percentage of neonates reaching toxic trough levels (> 5 mg/liter), from 40 to 76% to 14 to 25%, while still reaching efficacy targets compared to the results of current dosing regimens. Based on this study, a 12-h increase in the amikacin dosing interval in neonates with PATH is proposed to correct for the reduced clearance, yielding safe and effective exposures. As amikacin is renally excreted, further studies into other renally excreted drugs may be required, as their clearance may also be impaired.
机译：预计氨基糖苷药代动力学（PK）将用围产期窒息治疗治疗性低温（路径）的新生儿。已经提出了几种Amikacin给药指导因素用于治疗新生儿（可疑）败血症;但是，无提供路径情况的调整。因此，我们旨在量化NeoNates与途径与径向的氨基辛PK的差异，以提出合适的给药推荐。基于Amikacin治疗药物监测数据回顾性地从带有路径的新生儿收集的数据，结合发表的数据集，我们通过使用人口建模来评估路径对Amikacin PK的影响。蒙特卡罗和随机仿真进行了根据当前指南给药后，在给药后的新生儿中建立Amikacin暴露，并根据提出的模型衍生给药指导。氨基辛清除率下降40.6％，具有路径的新生儿，分布量没有变化。模拟表明，增加了12小时的剂量间隔导致新生儿达到有毒槽水平（> 5mg /升）的百分比减少，从40〜76％到14％至25％，同时仍然达到疗效目标相比当前剂量方案的结果。基于该研究，提出了具有路径的新生儿中的Amikacin剂量间隔12-H增加，以校正降低的间隙，产生安全和有效的暴露。由于Amikacin被肾外排出，因此可能需要进一步研究其它肾脏排出的药物，因为它们的间隙也可能受损。

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