Prior and Concomitant Medications in Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants

Prior and Concomitant Medications data
Study Description
The primary objective of this prospective, open-label, multi-center, pharmacokinetic (PK) study was to evaluate the PK and safety of IV metronidazole in premature infants <32 weeks gestational age with suspected serious infection. There were 24 participants enrolled in two age groups based on postnatal age. Each participant received metronidazole and was included in the PK population. Plasma PK was evaluated using a limited sampling scheme. A new dosing strategy based on PMA was developed to account for developmental changes in metronidazole disposition as well as for simplicity in clinical application. The dosing of 7.5 mg/kg Q12 hours in infants PMA <34 weeks and 7.5 mg/kg Q8 hours in infants with a PMA 34-40 weeks, with a loading dose of 15 mg/kg for both age cohorts would achieve therapeutic metronidazole concentrations in the majority (>75%) of infants <90 days of age. In addition, metronidazole was well tolerated in this open-label study. None of the AEs and SAEs reported was related to study drug. Premature infants <32 weeks gestation with suspected serious infection

既往与合并用药数据集
研究概况
本项前瞻性、开放标签、多中心药代动力学（pharmacokinetic, PK）研究的主要目的，是评估妊娠龄<32周的疑似重症感染早产儿静脉用甲硝唑的药代动力学特征与安全性。本研究共纳入24名受试者，按出生后年龄分为两个年龄组。所有受试者均接受甲硝唑治疗，且均被纳入PK分析人群。本研究采用有限采样方案对血浆药代动力学进行评估。本研究开发了一种基于校正胎龄（postmenstrual age, PMA）的全新给药方案，既可以适配甲硝唑体内处置过程的发育变化，也能简化临床应用流程。对于校正胎龄<34周的患儿，给予7.5 mg/kg、每12小时一次的给药方案；对于校正胎龄34~40周的患儿，给予7.5 mg/kg、每8小时一次的给药方案；两个年龄队列均给予15 mg/kg的负荷剂量。该方案可使绝大多数（>75%）<90日龄的患儿达到甲硝唑治疗浓度。此外，本项开放标签研究中，甲硝唑的耐受性良好。所有报告的不良事件（adverse events, AE）与严重不良事件（serious adverse events, SAE）均与研究药物无关。疑似重症感染的妊娠龄<32周早产儿