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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen
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Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen

机译：NeoNates中需要较大剂量的vancomycin，具有接受吲哚美辛与布洛芬接受吲哚美辛的新生儿

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Ibuprofen and indomethacin are commonly used to induce ductus arteriosus closure in preterm neonates. Our group previously reported that ibuprofen decreased vancomycin clearance by 16%. In this study, we quantified the impact of indomethacin coadministration on vancomycin clearance by extending our vancomycin population pharmacokinetic model with a data set containing vancomycin concentrations measured in preterm neonates comedicated with indomethacin. The modeling data set includes concentration-time data of vancomycin administered alone or in combination with either ibuprofen or indomethacin collected in the neonatal intensive care units of UZ Leuven (Leuven, Belgium) and Sao Francisco Xavier Hospital (Lisbon, Portugal). The derived vancomycin pharmacokinetic model was subsequently used to propose dose adjustments that yield effective vancomycin exposure (i.e., area under the concentration-time curve from 0 to 24 h [AUC(0-24)] between 300 to 550 mg"h/liter, with a probability of <0.1 of subtherapeutic exposure) in preterm neonates with patent ductus arteriosus. We found that indomethacin co-administration reduced vancomycin clearance by 55%. Model simulations showed that the most recent vancomycin dosing regimen, which was based on an externally validated model, requires 20% and 60% decreases of the loading and maintenance doses of vancomycin, respectively, when aiming for optimized exposure in the neonatal population. By analyzing vancomycin data from preterm neonates comedicated with indomethacin, we found a substantial decrease in vancomycin clearance of 55% versus a previously reported 16% for ibuprofen. This decrease in clearance impacts vancomycin dosing, and we anticipate that other drugs eliminated by glomerular filtration are likely to be affected to a similar extent as vancomycin.
机译：布洛芬和吲哚美辛通常用于诱导早产新生儿的导管蛛网闭合。我们的小组以前据报道，布洛芬降低了万古霉素清除率为16％。在这项研究中，我们通过将万古霉素群体药代动力学模型延长含有含有吲哚美辛的早产儿测量的万古霉素浓度的数据集来量化吲哚美辛共同素对万古霉素清除的影响。建模数据集包括单独施用的万古霉素的浓度数据，或者与在UZ Leuven（Leuven，Belgium）和Sao Francisco Xavier医院（Lisbon，葡萄牙）的新生儿重症监护单位中收集的布洛芬或吲哚美辛。随后使用衍生的万古霉素药代动力学模型用于提出产生有效的万古霉素暴露的剂量调节（即，在浓度 - 时间曲线下的面积为0至24小时[AUC（0-24）] 300至550mg“H /升，用副本暴露的概率<0.1的次管暴露，用专利导管血管术。我们发现吲哚美辛的共同给药减少了万古霉素清除55％。模拟模拟表明，最近的万古霉素给药方案，这是基于外部验证的型号，旨在在新生儿群体中的优化暴露时，载重霉素的加载和维护剂量分别需要20％和60％。通过分析来自吲哚美辛的早产新生儿的万古霉素数据，我们发现万古霉素清除的大量减少55％与先前报告的布洛芬对16％的人进行了16％。这种间隙影响了万古霉素给药，我们预计其他药物消除通过肾小球过滤术后可能受到类似程度的影响作为万古霉素。

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