Protocol Deviation in Safety and Pharmacokinetics of Multiple Dose Metronidazole in Premature Infants

Protocol Deviation 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

方案偏离数据
研究概况
本项前瞻性、开放标签、多中心药代动力学（pharmacokinetics，PK）研究的主要目的，为评估静脉输注甲硝唑用于胎龄小于32周、疑似严重感染早产儿的药代动力学特征与安全性。本研究按出生后年龄划分为两个年龄组，共纳入24名受试者，所有受试者均接受甲硝唑治疗并被纳入药代动力学分析人群。研究采用有限采样方案评估血浆药代动力学特征。基于校正胎龄（postmenstrual age，PMA）开发了全新给药策略，既可适配甲硝唑体内处置过程的发育变化，又可简化临床应用流程。校正胎龄小于34周的早产儿给予7.5 mg/kg、每12小时一次给药，校正胎龄34~40周的早产儿给予7.5 mg/kg、每8小时一次给药；两个年龄组均给予15 mg/kg负荷剂量，该方案可使75%以上年龄小于90天的早产儿达到甲硝唑治疗浓度。此外，本项开放标签研究中甲硝唑耐受性良好，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。胎龄小于32周的疑似严重感染早产儿